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Littérature scientifique sur le sujet « Analoghi insulina »

Auteur : Grafiati
Publié le 9 mars 2023
Mis à jour le 10 mars 2023

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Articles de revues sur le sujet "Analoghi insulina"

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Valenzano, M. « Insulin : 100 years but not over the hill ! A treatment with potential for renewal ». Journal of AMD 25, no 2 (juillet 2022) : 97. http://dx.doi.org/10.36171/jamd22.25.2.

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L’insulina è ancora un trattamento fondamentale per molti pazienti con diabete. A un secolo dalla sua scoperta, nuovi analoghi sono in procinto di essere disponibili così da potenziare ulteriormente la farmacocinetica e la farmacodinamica della molecola, sia in termini di effetto sostenuto (per l’insulina basale settimanale) che di velocità d’azione (per gli analoghi ultrarapidi). Inoltre, penne intelligenti e nuovi dispositivi agevoleranno la somministrazione di insulina, fornendo anche supporto digitale per il calcolo della dose, il monitoraggio e l’analisi delle iniezioni e, si spera, saranno utili per l’economia e l’ecosistema del pianeta. Infine, la ricerca futura è orientata allo sviluppo dell’insulina orale e dell’insulina intelligente e glucosensibile. La storia dell’insulina è tuttora in fieri e riserverà ancora molte novità. PAROLE CHIAVE insulina; insulina basale settimanale; insulina ultrarapida; penna intelligente; insulina intelligente.
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Toni, Roberto. « Tipi di insulina e suoi analoghi a 100 anni dalla scoperta ». L'Endocrinologo 22, no 1 (février 2021) : 63–67. http://dx.doi.org/10.1007/s40619-021-00832-5.

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Veltroni, Alessio, Elisa Cosaro et Maria Vittoria Davì. « Caratteristiche clinico-patologiche, gestione clinica e prognosi dell’insulinoma maligno : studio multicentrico italiano ». L'Endocrinologo 22, no 2 (17 mars 2021) : 139–43. http://dx.doi.org/10.1007/s40619-021-00843-2.

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SommarioL’insulinoma maligno è un tumore neuroendocrino pancreatico estremamente raro ed è associato a una severa sindrome ipoglicemica che impatta negativamente sulla qualità di vita e sulla sopravvivenza dei pazienti affetti. La gestione terapeutica dell’insulinoma maligno è complessa sia per il controllo delle crisi ipoglicemiche, sia per il controllo della crescita tumorale. La sindrome ipoglicemica rappresenta una sfida terapeutica per l’endocrinologo in quanto spesso non è responsiva alla terapia medica sintomatica, in particolare al diazossido utilizzato in monoterapia o associato agli analoghi della somatostatina. Everolimus ha un ruolo nel trattamento delle crisi ipoglicemiche refrattarie da insulinoma maligno sia per l’azione di inibizione del rilascio di insulina che di insulino-resistenza. La chirurgia con approccio curativo dell’insulinoma maligno è raramente perseguibile a causa della diffusione metastatica, mentre la chirurgia a scopo di debulking può essere presa in considerazione in casi selezionati sia per il controllo sintomatico sia perché può aumentare l’efficacia delle terapie sistemiche o locoregionali. La terapia radiometabolica con analoghi caldi della somatostatina rappresenta un’opzione terapeutica nei pazienti con tumori a elevata espressione dei recettori della somatostatina sia per il controllo della sintomatologia che della crescita tumorale, sebbene l’esperienza negli insulinomi maligni sia piuttosto scarsa. Data la rarità della malattia, sono disponibili in letteratura solo descrizioni di singoli casi o studi condotti su casistiche limitate; pertanto, è difficile stabilire la sequenza terapeutica più efficace in questi casi. Recentemente è stato condotto uno studio multicentrico italiano, in 13 centri di riferimento, focalizzato sulle caratteristiche clinico-patologiche, sulle modalità di trattamento e sui fattori prognostici che condizionano decorso ed esito dell’insulinoma maligno allo scopo di individuare una strategia terapeutica mirata basata su criteri razionali ed evidenze cliniche. In questa rassegna verranno descritti i principali risultati dello studio che comprende una casistica tra le più ampie finora pubblicate.
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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder et Rashem Mothilal. « A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part two : Insulin degludec vs. insulin glargine U300 ». South African Family Practice 60, no 4 (28 août 2018) : 7–12. http://dx.doi.org/10.4102/safp.v60i4.4903.

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Glucose clamp studies form an integral part of the early development of insulin therapies. Data generated in these studies are used to establish pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the agents, but methodological differences confound comparison of results from different glucose clamp studies. The first part of this series on glucose clamp studies discussed practical tips for the interpretation of glucose clamp studies. The second part of the series compares the PK/PD profiles of longer-acting basal analogue insulins, insulin degludec (IDeg) and insulin glargine U300 (Gla-300). The patient populations for glucose clamp studies with these analogue insulins differ, and therefore direct comparison of the data is not always possible. The maximum duration of action of IDeg is reported as 42 h and that of Gla-300 as 36 h, translating to 24 h coverage. The plasma insulin concentration of IDeg is 56 times that of Gla-300. Results from phase III clinical trials for these analogue insulins confirm the predictability and low within-subject variability observed in glucose clamp studies. Insight into the PK/PD profiles of longer-acting basal analogue insulins allows the treating physician to utilise these characteristics to optimise the treatment of their patients with diabetes.
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Veikko, Dr, et A. Koivisto. « Analogi insulina ». Diabetes mellitus 2, no 4 (15 décembre 1999) : 29–34. http://dx.doi.org/10.14341/2072-0351-6130.

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Zac-Varghese, Sagen, Bev Summerhayes et Peter Winocour. « Managing type 1 diabetes in frailty ». BMJ Case Reports 15, no 12 (décembre 2022) : e253779. http://dx.doi.org/10.1136/bcr-2022-253779.

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Managing type 1 diabetes in frail elderly people can be logistically challenging, particularly for those living alone. District nurse visits are unpredictable and coincide poorly with meal time insulin regimes. Elderly people, particularly those with dementia, have variable oral intake and activity. For some, poor glycaemic control leads to frequent and prolonged inpatient admissions. The use of technology, such as flash glucose monitoring, and the use of analogue insulins can be helpful in this setting. Increased monitoring enables more accurate titration of insulin doses and the information can be accessed by healthcare professionals and carers remotely. Longer lasting analogue insulins allow for a greater margin of error in the timing of insulin administration.
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Greeff, Oppel B. W., Jacob John Van Tonder, Kershlin Naidu, Alicia McMaster, Alet Van Tonder et Rashem Mothilal. « A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part one : The principles of glucose clamp studies ». South African Family Practice 60, no 3 (12 juillet 2018) : 8–12. http://dx.doi.org/10.4102/safp.v60i3.4874.

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Glucose clamp studies are used to determine pharmacokinetics (PK) and pharmacodynamics (PD) of analogue insulins. With the development of longer-acting basal analogue insulins, including glargine 300 (Gla-300) and insulin degludec (IDeg), results from numerous glucose clamp studies are readily available. However, interpreting PK/PD profiles in a scientifically sound manner can be a challenging feat. This is the first in a series of publications that will suggest practical tips for interpreting and comparing results from glucose clamp studies. Variations in the glucose clamp methodology, duration of clamp studies and glucose clamp targets influence the study design and results significantly. Selection of study populations, including healthy patients or patients with Type 1 or 2 diabetes mellitus, has important implications. The dose of study insulin should reflect that of the general treatment population, and ideally steady-state conditions should be used. During the study the plasma insulin concentration and glucose infusion rate describe the pharmacokinetics and pharmacodynamics of the study insulin. With these practical tips in mind, results of glucose clamp studies can be interpreted in a scientifically correct manner. The next article in this series will discuss the interpretation of PK/PD profiles using two newly developed longer-acting basal analogue insulins: Gla-300 and IDeg.
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Mbanya, Jean Claude, Juergen Sandow, Wolfgang Landgraf et David R. Owens. « Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy ». European Endocrinology 13, no 01 (2017) : 21. http://dx.doi.org/10.17925/ee.2017.13.01.21.

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Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications.
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Noor Wafaa Hashim, Kadhim Ali Kadhim et Abbas Mahdi Rahmah. « Effect of human insulin and insulin analogue on some inflammatory markers and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents ». Al Mustansiriyah Journal of Pharmaceutical Sciences 21, no 2 (19 avril 2022) : 9–14. http://dx.doi.org/10.32947/ajps.v21i2.804.

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Background: Both human insulin and insulin analogue used in the treatment of type 1 diabetes mellitus. The modification in amino acids sequences of human insulin lead to produce analogue form which have a pharmacokinetic and pharmacodynamics effect near to normal human endogenous insulin release. Aim of study: This study designed to compare between the effect of each type of insulin on high sensitive C-reactive protein and interleukin-6 and total antioxidant capacity in a sample of Iraqi type 1 diabetic children and adolescents. Study design: The study was enrolled on fifty-one Iraqi type 1 diabetic children and adolecence age range (6-18) year. The patients allocated into two groups, Group (1) includes 20 patients assigned to receive conventional human insulin (regular and NPH), and Group (2) includes 20 patients assigned to receive insulin analogue (insulin aspart and glargine) for three months. The inflammatory and antioxidant markers measured at baseline and after three months of intervention. Results: After three months of treatment, both insulin groups did not affect high sensetive C_reactive protein (hs-CRP) significantly from baseline to 3 months. Only insulin analogue reduced Interleukin-6 (IL-6) significantly, while human insulin reduced level of IL-6 but it was not statistically significant. Both therapies reduced total antioxidant capacity (TAOC) significantly; however, insulin analogue had higher reduction percentage (15.1% vs. 5.7%) compared to the conventional insulin. Conclusion: Only insulin analogue reduced IL-6 significantly. Both types of insulins did not effect on hs-CRP. Both therapies reduce TAOC significantly.
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AUTHIER, François, Gianni M. Di GUGLIELMO, Gillian M. DANIELSEN et John J. M. BERGERON. « Uptake and metabolic fate of [HisA8,HisB4,GluB10,HisB27]insulin in rat liver in vivo ». Biochemical Journal 332, no 2 (1 juin 1998) : 421–30. http://dx.doi.org/10.1042/bj3320421.

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Receptor-mediated endocytosis and subsequent endosomal proteolysis of [125I]TyrA14-[HisA8,HisB4,GluB10,HisB27]insulin ([125I]TyrA14-H2 analogue), an insulin analogue exhibiting a high affinity for the insulin receptor, has been studied in liver parenchymal cells by quantitative subcellular fractionation and compared with that of wild-type [125I]TyrA14-insulin. Whereas the kinetics of uptake of the H2 analogue by liver was not different from that of insulin, the H2 analogue radioactivity after the 2 min peak declined significantly more slowly. A significant retention of the H2 analogue compared with insulin in both plasma membrane and endosomal fractions was observed and corresponded to decreased processing and dissociation of the H2 analogue. Cell-free endosomes preloaded in vivo with radiolabelled ligands and incubated in vitro processed insulin and extraluminally released insulin intermediates at a 2–3-fold higher rate than the H2 analogue. In vitro proteolysis of both non-radiolabelled and monoiodinated molecules by endosomal lysates showed a decreased response to the endosomal proteolytic machinery for the H2 analogue. However, in cross-linking and competition studies the H2 analogue exhibited an affinity for insulin-degrading enzyme identical with that of wild-type insulin. Brij-35-permeabilized endosomes revealed a 2-fold higher rate of dissociation of insulin from internalized receptors compared with the H2 analogue. After the administration of a saturating dose of both ligands, a rapid and reversible ligand-induced translocation of insulin receptor was observed, but without receptor loss. The H2 analogue induced a higher receptor concentration and tyrosine autophosphorylation of the receptor β subunit in endosomes. Moreover, a prolonged temporal interaction of the in vivo injected H2 analogue with receptor was observed by direct binding assays performed on freshly prepared subcellular fractions. These results indicate that endosomal proteolysis for the H2 analogue is slowed as a result of an increased residence time of the analogue on the insulin receptor and a low affinity of endosomal acidic insulinase for the dissociated H2 molecule.
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Thèses sur le sujet "Analoghi insulina"

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PEROTTI, MARIO. « EFFICACIA DEL PASSAGGIO A DEGLUDEC DA UN’ALTRA INSULINA BASALE (GLARGINE/ DETEMIR) IN UNA COORTE DI PAZIENTI CON DIABETE MELLITO TIPO 1 ( DMT1) IN CONDIZIONI DI REALE PRATICA CLINICA ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241121.

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La terapia del diabete tipo 1 può oggi essere più flessibile e personalizzata grazie alla disponibilità di numerosi tipi di insulina che differiscono tra loro per la farmacocinetica (inizio, picco e durata di azione). Il miglior controllo glicometabolico può essere ottenuto attraverso una terapia multiniettiva secondo uno schema basal-bolus, il quale prevede 3 somministrazioni preprandiali di un analogo rapido, che esprime meglio la fisiologica secrezione insulinica determinata dai pasti e da 1 iniezione di insulina ad azione lenta, necessaria per rispondere al fabbisogno insulinico nei periodi di digiuno (interprandiale e notturno). Il raggiungimento di un controllo glicemico ottimale mediante trattamento insulinico intensivo determina un riduzione del rischio di complicanze micro e macrovascolari, ma conduce inevitabilmente a un incremento dell’incidenza di ipoglicemie, con conseguenze potenzialmente negative per il sistema cardiovascolare e neurologico. Ottimizzare la terapia farmacologica mediante l’utilizzo di nuovi analoghi dell’insulina ad azione lenta in grado di offrire un minore rischio di ipoglicemia rappresenta un punto di fondamentale importanza. Insulina degludec presenta molte delle caratteristiche che definiscono il profilo ideale di un’insulina basale. Dopo la somministrazione nel sottocute, grazie alla particolare ingegneria chimica, degludec viene assorbita in modo continuo e uniforme con un effetto ipoglicemizzante stabile e una durata di azione che supera le 42 ore. Dopo circa tre giorni di terapia è possibile raggiungere lo steady state condizione farmacocinetica in cui i livelli circolanti di insulina si mantengano stabili riducendo così la variabilità day-to day L'utilizzo di degludec è stato ampiamente analizzato nel corso di studi clinici randomizzati ( RCT) sia in pazienti con diabete mellito tipo I sia in pazienti con diabete mellito tipo II. I risultati mostrano una non inferiorità di degludec rispetto a glargine in termine di target glicemici, ma una superiorità di degludec rispetto a glargine in termini di riduzione degli episodi di ipoglicemia soprattutto notturni. Tuttavia il contesto clinico di uno studio randomizzato può non essere completamente riproducibile nella pratica clinica quotidiana. Obiettivo di questo studio retrospettivo è la valutazione dell’efficacia clinica di degludec in una coorte di pazienti affetti da diabete mellito tipo 1 precedentemente trattati con diverso analogo lento ( glargine o detemir) nella pratica clinica quotidiana di real-life. I risultati di questo studio mostrano un impatto positivo di degludec nella gestione terapeutica di pazienti con diabete mellito tipo 1 in linea con precedenti studi clinici randomizzati . Il passaggio a degludec da un altro analogo basale ( glargine o detemir) è in grado di migliorare il controllo glicemico, con una riduzione media dei valori di HbA1c di 0,20 % [-0,24;-0.17] a 6 mesi rispetto al basale (p <0.001). Inoltre i dati descritti in questo lavoro hanno evidenziato una riduzione del rischio di ipoglicemia sia totale ( rate ratio 0,79 [0,69: 0,89]), sia notturna (rate ratio 0,54 [0,42; 0,69]) sia grave (rate ratio 0,15 [0,09; 0,24]) a 6 mesi dalla modifica di terapia (p <0.001). Tale significatività rimane per tutto il periodo di follow-up di 12 mesi. Infine dopo 6 mesi di terapia con degludec, la dose totale di insulina giornaliera è diminuita del 11% rispetto al basale (p <0,001). Sulla base di questi dati, possiamo affermare che la terapia insulinica con degludec rappresenta un valido strumento terapeutico nella pratica clinica quotidiana, in grado di migliorare il compenso glicemico e la qualità di vita dei pazienti, favorendo così il raggiungimento di obiettivi glicemici più ambiziosi.
Type 1 diabetes (DMT1) leads to absolute insulin deficiency due to immunologic destruction of the islet cells. Therefore affected patients need lifelong insulin treatment. Newer therapies for type 1 diabetes are aimed at developing insulin delivery systems that mimick normal physiology, identifying newer insulins that mimick endogenous insulin. To reproduce physiologic insulin secretion, both long- and short-acting insulins are used. Long-acting insulin, given at bedtime, suppresses glucose output from the liver overnight and provides basal insulin between meals; bolus doses of short-acting insulin modulate glucose excursions associated with carbohydrate consumption. Optimal glycemic control is necessary to reduce the risk for diabetes complications. However, tight glucose control carries a risk for hypoglycemia. Hypoglycemia may accelerate the vascular complications of diabetes by increasing platelet aggregation, leading to higher cardiovascular risk and all-cause mortality. Even brief hypoglycemia can cause profound dysfunction of the brain. Insulin administration by subcutaneous route has intrinsic limitations that, together with the pharmacokinetic (PK) profile of insulin formulations, do not reproduce the physiological patterns of insulin secretion. Insulin degludec (IDeg) is an ultra-long insulin analog that has unique pharmacokinetic and pharmacodynamic properties with a half-life of more than 24 h and a duration of action of more than 42 h. Compared to insulin glargine , the insulin degludec glucose-lowering action at steady state shows four time lower day-to day variability. Randomized clinical studies of degludec have shown a reduction in nocturnal hypoglycemia compared to insulin glargine. Given this background, IDeg is an ultra-long insulin analog that exhibits low intra-individual variability and whose efficacy is comparable to IGlar, but which presents as advantages flexibility in dose timing and lower risk of hypoglycemia, benefits that may impact quality of life and adherence to therapy. In Europe data on the use or effect of degludec in the general diabetes population not exist yet. Thus collection of data under routine clinical practice is highly warranted in order to access the effectiveness of degludec in real-life clinical setting. Aim of this retrospective non interventional study is to evaluate the clinical effectiveness of switching to IDeg in insulin treated patients with DMT1 under condition of routine clinical care. In all patients (n: 900), basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. HbA1c decreased by -0.20 % [-0.24; -0.17%] at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.
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Elamin, Ahmed Abu Baker. « Studies on the short-acting insulin analogue lispro ». Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310125.

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Verchere, Cameron Bruce. « Control of insulin secretion from the perfused rat pancreas : effects of acetylcholine and a somatostatin analog, SMS 201-995 ». Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26657.

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The effect of varying concentrations of glucose or the gastrointestinal hormones, gastric inhibitory polypeptide (GIP) and somatostatin (SS-14), on the in vitro immunoreactive insulin (IRI) response to the parasympathetic neurotransmitter, acetylcholine (ACh) was investigated. The isolated, vascularly perfused rat pancreas was used in all experiments. Acetylcholine (1.0 µM) did not stimulate IRI secretion in the presence of 2.2 mM glucose. However, in the presence of 4.4, 6.6, or 8.9 mM glucose, ACh (1.0 µM) potently stimulated IRI secretion (approximately fourfold). At a higher glucose concentration (17.8 mM), the IRI response to ACh was reduced. GIP also potentiated the IRI response to 1.0 µM ACh. This potentiation was most marked in the presence of 1.0 nM GIP, whereas the effect of concomitant infusion of 0.2 nM GIP and 1.0 µM ACh was only slightly greater than additive. SS-14 potently inhibited ACh-stimulated IRI secretion. These results demonstrated the glucose dependency of cholinergically stimulated IRI secretion, and that physiological levels of glucose and GIP increased B-cell sensitivity to cholinergic stimulation. It was suggested that the parasympathetic stimulation of IRI secretion associated with food intake could be affected by postprandial increases in glucose, GIP, and SS-14. The idea that endogenously released somatostatin may have influenced glucose or GIP-stimulated IRI secretion was not supported by the present experiments, since neither glucose (8.9 mM) nor GIP (2.0 nM) were found to have a significant effect on the release of pancreatic somatostatin-like immunoreactivity (SLI). Both atropine (1.0 µM) and hexamethonlum (100 µM) inhibited the IRI response to ACh. This suggested that the parasympathetic stimulation of IRI secretion was mediated not only by muscarinic receptors on the B-cell, but also by nicotinic receptors on intrapancreatic ganglia. Neither atropine nor hexamethonlum had a significant effect on glucose- or GIP-stimulated IRI secretion, indicating that the IRI response to these stimuli was not mediated by cholinergic receptors. Both SS-14 and the synthetic somatostatin analog SMS 201-995 (SMS; Sandostatin®) inhibited IRI secretion stimulated by 8.9 mM glucose, 2.0 nM GIP, or 1;.0 µM ACh, but not 17.8 mM glucose. The most potent inhibition by both SS-14 and SMS was observed in the presence of the weakest IRI stimuli (8.9 mM glucose and 1.0 µM ACh). These results suggested that the inhibitory effects of somatostatin on the B-cell could be overcome by the presence of strong stimuli. In addition, the inhibitory effects of the native hormone and the analog were found to be approximately equipotent (weight basis), indicating that the increased potency of SMS previously observed in vivo was due to its longer half-life in plasma, and not due to a more potent direct effect on the B-cell.
Medicine, Faculty of
Cellular and Physiological Sciences, Department of
Graduate
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Louafi, Fethi. « Role of retinoic acid or vitamin D analogue in models of human keratinocyte apoptosis : interactions with the IGF system ». Thesis, University of Warwick, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269235.

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Gagnon-Auger, Maude. « Améliorer la pharmacocinétique de l’insuline analogue ultrarapide chez des sujets obèses et diabétiques de type 2 ». Thèse, Université de Sherbrooke, 2015. http://hdl.handle.net/11143/11616.

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Résumé: Comparées aux classiques insulines humaines régulières (IHR), les insulines analogues ultrarapides (IAUR) ont été conçues pour mieux synchroniser le pic insulinémique avec l’absorption du repas. Le progrès a été démontré chez les patients diabétiques de type 1, mais le contrôle glycémique s’est peu ou pas amélioré chez les patients diabétiques de type 2 (DT2), qu’ils soient sous IAUR ou IHR. Or ces patients constituent 75 % des utilisateurs d’insuline. L’utilité des IAUR est donc toujours débattue. La dose (donc le volume) injectée et le flot sanguin dans le tissu adipeux sous-cutané (FSTA) sont les facteurs majeurs de l’absorption de l’insuline. Les patients DT2, résistants à l’insuline, s’injectent des doses importantes et leur FSTA est de 50 à 70 % plus faible que celui des sujets sains de poids normal (PN). Nous avons montré que l’absorption sous-cutanée des IAUR est diminuée chez les sujets obèses et DT2 (ODT2) par rapport aux sujets PN, que le volume injecté avait un effet délétère additionnel et que le FSTA peut être augmenté de façon pharmacologique avec un agent vasoactif (AV) chez des sujets résistants à l’insuline. Nous suggérons que l’ajout d’un AV à une IAUR va augmenter le FSTA au site d’injection et donc améliorer sa pharmacocinétique (PK) et sa pharmacodynamie (PD). Pour vérifier cette hypothèse, nous avons 1) évalué la réponse du FSTA à 4 AV chez des sujets PN, obèses non-diabétiques et ODT2; 2) évalué la PK/PD et la biodisponibilité de l’IAUR lispro ± AV chez des sujets ODT2; et 3) caractérisé l’expression des cibles des AV dans le tissu adipeux sous-cutané chez les sujets énumérés en 1). Les 4 AV ont augmenté le FSTA des sujets ODT2, mais moins que celui des autres sujets. L’occurrence de la raréfaction et/ou dysfonction microvasculaire chez les sujets ODT2 pourrait expliquer l’hyporéactivité vasculaire aux AV testés. Le plus actif des AV chez les sujets ODT2 a été ajouté à l’IAUR lispro pour améliorer sont absorption sc. Les PK/PD ont été améliorées seulement chez les sujets ODT2 avec une hémoglobine glycosylée A1c ≥ 8 %; c’est-à-dire 4 sujets sur 8. Chez ces derniers, l’absorption de 30 U + AV a été plus rapide de 14 et 71 min à 20 et 80 % de l’aire sous la courbe totale de la lispro plasmatique, respectivement. Chez les 4 autres sujets ODT2, l’absorption de la lispro semble s’être détériorée avec l’AV. Une interaction chimique a peut-être eu lieu entre l’AV et la lispro, ce qui aurait perturbé son absorption. Selon nos résultats, le niveau de contrôle du diabète, le volume d’injection et les caractéristiques chimiques de l’AV seraient des modulateurs de l’efficacité du concept IAUR + AV. Il nous faut maintenant déterminer l’impact de ces facteurs sur la capacité d’un AV à améliorer l’absorption sc de l’IAUR chez les sujets ODT2.
Abstract: Compared to classic regular human insulin (RHI), short-acting insulin analogues were designed to better synchronize plasma insulin increase to food absorption. Although improvements were noted in subjects with type 1 diabetes, slight to no improvement in glycemic control were observed in subjects with type 2 diabetes (T2D) using SAIA instead of RHI. Nevertheless, they represent 75 % of all insulin users. Consequently, the relative useful-ness of SAIA in T2D patients is currently hotly debated. Injected volume and subcutaneous (sc) adipose tissue blood flow (ATBF) are two main factors involved in insulin absorption. In fact, T2D patients use large doses of insulin because of their resistance to insulin and have an ATBF 50 to 70 % lower than lean healthy subjects. We already showed that SAIA absorption is decreased in obese T2D (OT2D) subjects compared to normal weight healthy subjects and that volume has additional detrimental effects. We also showed that ATBF can be increased pharmacologically with vasoactive agents (VA) in healthy and insulin-resistant subjects. Then we suggest that in OT2D subjects, addition of VA to SAIA preparations will locally increase ATBF, improve insulin sc absorption (Pharmacokinetic - PK) and bioavailability, thus insulin hypoglycemic effect (Pharmacodynamic - PD). To test this hypothesis, we 1) assessed ATBF response of 4 selected VA within three experimental groups (normal weight, obese non-diabetic and OT2D subjects); 2) evaluated insulin PK/PD and bioavailability improvement in OT2D subjects after the addition of the best VA to SAIA lispro and 3) characterized expression of selected VA targets in sc adipose tissue biopsies, within equivalent experimental groups, and compared results with ATBF responses. All 4 VA were able to increase ATBF of OT2D subjects but in a less extend than other subjects. The occurrence of microvascular rarefaction and/or dysfunction in OT2D subjects can explain the hyporeactivity to tested VA. Nevertheless, one VA among others was shown more effective to increase ATBF in OT2D subjects and was then tested (mixed) with SAIA lispro. With the AV, PK/PD were improved only in OT2D subjects with A1c glycated hemoglobin ≥ 8 %; 4 subjects on 8. The sc absorption of 30 U + VA was faster by 14 and 71 min for respectively 20 and 80 % of the total area under the lispro plasmatic curve. But the sc absorption with VA appeared blunted with the other subjects. Maybe detrimental chemical interactions occurred between the VA and lispro, which could impede absorption. Our results suggest that diabetes control state, injection volume, and VA chemical characteristics influence the efficacy of our SAIA + VA concept. Further tests are needed to seize the impact of these factors on VA effectiveness in sc absorption improvement of SAIA in OT2D subjects.
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Glidden, Michael D. II. « Single-chain insulin analogs as ultra-stable therapeutics and as models of protein (mis)folding : stability, structure, dynamics, and function of novel analogs ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1522270994798884.

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Duarte, Felipe Henning Gaia. « Síndrome da apnéia do sono na acromegalia : impacto do tratamento sobre o metabolismo dos carboidratos ». Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-19092011-152108/.

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Introdução: A acromegalia é uma doença rara, caracterizada pela produção aumentada de hormônio do crescimento, causada geralmente por um adenoma hipofisário, ocasionando uma série de comorbidades como apneia do sono e resistência insulínica que acarretam um aumento na mortalidade e redução da expectativa de vida. Objetivo: O objetivo deste estudo foi avaliar o impacto da terapêutica da apneia do sono com um dispositivo de pressão positiva contínuas nas vias aéreas (CPAP) e avaliar o impacto desta terapêutica na resistência insulínica pela realização do clamp euglicêmico hiperinsulinêmico (CEH). Pacientes: De 156 acromegálicos regularmente atendidos na unidade de Neuroendocrinologia do HC-FMUSP, foram selecionados 12 indivíduos com apneia do sono de moderada a grave em uso de análogos da somatostatina (AS). Método: Os pacientes foram randomizados em dois grupos com seis integrantes. O grupo A iniciou o tratamento com CPAP, e o grupo B, um adesivo dilatador nasal com efeito de placebo. A avaliação basal incluiu a polissonografia, determinação do GH, IGF-1, HbA1c, ácidos graxos livres, lípides, CEH, bem como os índices de resistência periférica à insulina (HOMA, HOMA2 e QUICKI). Após 3 meses de tratamento, os pacientes foram reavaliados pelos mesmos exames, sendo trocado o tratamento entre os grupos e feita nova avaliação, após mais 90 dias. Resultados: Analisando os resultados finais de todos os pacientes que fizeram uso do CPAP, foi observada uma redução significante na resistência periférica à insulina, verificada pelo índice de sensibilidade derivado do clamp (ISCLAMP, pré e pós- CPAP, 3,83 versus 6,11, p=0,032). Esta redução não foi observada no grupo que fez uso do adesivo nasal (ISCLAMP, pré e pós-adesivo, 5,53 versus 5,19, p=0,455). Não houve diferença significante nos níveis de lípides, HbA1c nem nos índices de resistência periférica à insulina. Conclusão: O tratamento da apneia do sono moderada a grave com CPAP, em pacientes acromegálicos em uso de AS, levou a uma redução da resistência periférica à insulina aferida pelo CEH, dado não observado por meio dos índices HOMA, HOMA2 e QUICKI
Introduction. Acromegaly is a rare disease, characterized by the production of high GH levels usually by pituitary adenoma leading to comorbidities as sleep apnea and insulin resistance, bringing increase of mortality and life span reduction. Objective: This study aims to assess the impact of treatment of sleep apnea with a continuous positive air pressure device (CPAP) on the insulin resistance by performing the hyperinsulinemic euglycemic clamp (HEC). Patients: From 156 acromegalic patients regularly attended on Neuroendocrine Unit of the Hospital das Clínicas, University of São Paulo Medical School, 12 subjects on somatostatin analogs (SA) harboring moderate to severe sleep apnea were selected. Methods: Patients were randomized in two groups of six subjects. Group A started treatment with CPAP while group B started treatment using a nasal dilator adhesive with placebo effect. Basal assessment included polysomnography, determination of GH, IGF-1, HbA1c, free fat acids, lipids assays, HEC as well as insulin resistance indexes (HOMA, HOMA2 and QUICKI). Patients were reevaluated after three months of treatment by the same tests and then the treatment was switched between groups with new assessment 90 days later. Results: A significant reduction on insulin resistance determined by the clamp derived sensibility index was observed after assessing the final data of all patients on CPAP (SICLAMP, pre and post CPAP, 3,83 versus 6,11, p=0,032). This reduction was not seen in the nasal dilator adhesive group (SICLAMP, pre and post adhesive, 5,53 versus 5,19, p=0,455). There was no significant difference on lipids, HbA1c or on peripheral insulin resistance indexes. Conclusion: CPAP treatment of acromegalic patients on AS with moderate to severe sleep apnea leaded to significant reduction on peripheral insulin resistance assessed by the HEC. HOMA, HOMA2 and QUICK did not detect this data
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Moolman, Lukas Johannes. « The effect of snacking on continuously monitored glucose concentrations in analogue insulin basal bolus treatment regimens ». Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/40694.

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Marsh, Andrew. « Characterisation of the type I IGF receptor binding surfaces of insulin-like growth factor 1 using protein engineering ». Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245705.

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Gagnon-Auger, Maude. « Réévaluation de la pharmacocinétique d'une insuline analogue ultrarapide chez des sujets obèses et diabétiques de type 2 ». Mémoire, Université de Sherbrooke, 2010. http://savoirs.usherbrooke.ca/handle/11143/4004.

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Les caractéristiques pharmacocinétiques des insulines analogues ultra-rapides (IAUR) furent établies chez des sujets de poids normal, sains ou diabétiques de type 1, et à partir de petites doses d'insuline (4-12 U). La taille de la dose injectée et le flot sanguin dans le tissu adipeux (FSTA) sont des facteurs très importants qui affectent l'absorption sous-cutanée de l'insuline. Cependant, chez les patients obèses et diabétiques de type 2 (DT2), les doses d'insulines injectées sont beaucoup plus importantes et leur FSTA de base est 50 à 70 % plus faible que chez un sujet sain de poids normal. Ce qui porte à croire que l'absorption de l'insuline est moins efficace chez ces patients. Notre objectif est de déterminer la pharmacocinétique et la pharmacodynamie d'une IAUR chez les patients DT2 obèses. Six sujets témoins sains et de poids normal reçurent 10 U d'IAUR lispro et 7 sujets DT2 obèses 10, 30 et 50 U. Après injection sous-cutanée, nous avons procédé à un clamp euglycémique. La lispro plasmatique fut mesurée par RIA spécifique.Les paramètres de cinétique et de dynamique obtenus chez nos sujets sains confirment ceux publiés précédemment. Nos résultats sont donc pleinement en accord avec la littérature. Lors de l'injection de petites doses (10 U) chez les sujets DT2 obèses, l'absorption de la lispro ne semble pas être altérée par rapport aux témoins : la constante d'absorption (ka), le temps au pic plasmatique de lispro (T[indice inférieur max]) et l'aire totale sous la courbe (AUC[indice inférieur 0-[infini]]) sont semblables à ceux des témoins. Cependant, chez les sujets DT2, l'augmentation de la dose injectée couduit [i.e. conduit] à une réduction de la ka et un retard du T[indice inférieur max]. Dans les paramètres de glucodynamie, des différences très significatives se manifestent entre les 2 groupes, avec une réponse à l'insuline retardée et réduite chez les sujets DT2. Avec l'injection de 10 U, le taux d'infusion maximal de glucose (GIR[indice inférieur max]) est 15 fois plus petit et le temps correspondant (tGIR[indice inférieur max]) a presque doublé. Dans ce même groupe, on note un délai qui augmente avec de la dose injectée : le tGIR[indice inférieur max] a doublé entre les doses de 10 et 50 U et se chiffre à 4 heures pour l'injection de 50 U. Cette étude suggère que dans l'application clinique, la taille des doses injectées doit être considérée et que la synchronisation entre l'injection d'une IAUR et la prise du repas chez les patients DT2 obèses doit être étudiée. Afin d'améliorer l'absorption de l'insuline chez nos sujets obèses et DT2, nous avons testé deux méthodes : ajouter un agent activateur de flot (AVD) à la lispro ou bien augmenter la concentration de l'insuline pour diminuer le volume de la dose injectée. L'ajout d'AVD a mené à des résultats surprenants : l'AUC, le pic plasmatique de lispro (C[indice inférieur max]), le GIR[indice inférieur max] et l'infusion totale de glucose (GI[indice inférieur tot]) ont augmenté de 3 fois. Cependant, la diminution du volume de la dose injectée n'a eût [i.e. eu] aucun effet notoire sur l'absorption de la lispro. D'autres études seront donc faites pour mieux caractériser l'effet de lAVD sur l'absorption sous-cutanée de l'insuline.
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Livres sur le sujet "Analoghi insulina"

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E, Warren, et National Co-ordinating Centre for HTA (Great Britain), dir. Systematic review and economic evaluation of a long-acting insulin analogue, insulin glargine. Tunbridge Wells : Gray Publishing on behalf of NCCHTA, 2004.

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Shukla, Vijay. Insulin lispro : A critical evaluation. Ottawa, Ont : Canadian Coordinating Office for Health Technology Assessment, 1999.

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Chapitres de livres sur le sujet "Analoghi insulina"

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Shoelson, Steven E., Claire S. Lynch, Swati Chatterjee, Manas Chaudhuri et You-Ming Feng. « Bpa-insulins : Photoactivatable analogs for identifying site-site interactions between insulin and the insulin receptor ». Dans Peptides, 57–59. Dordrecht : Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_16.

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Müller, Günter. « Insulin Analogs : Assessment of Insulin Mitogenicity and IGF-I Activity ». Dans Drug Discovery and Evaluation : Pharmacological Assays, 3119–66. Cham : Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-05392-9_71.

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Müller, Günter. « Insulin Analogs : Assessment of Insulin Mitogenicity and IGF-I Activity ». Dans Drug Discovery and Evaluation : Pharmacological Assays, 1–54. Berlin, Heidelberg : Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-27728-3_71-1.

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Slieker, L. J., G. S. Brooke, R. E. Chance, R. D. DiMarchi, L. Fan, J. A. Hoffman, D. C. Howey et al. « Insulin and IGF-I analogs : novel approaches to improved insulin pharmacokinetics ». Dans Peptides, 7–10. Dordrecht : Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-010-9066-7_2.

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Slieker, Lawrence J., Gerald S. Brooke, Ronald E. Chance, Li Fan, James A. Hoffmann, Daniel C. Howey, Harlan B. Long et al. « Insulin and IGF-I Analogs : Novel Approaches to Improved Insulin Pharmacokinetics ». Dans Advances in Experimental Medicine and Biology, 25–32. Boston, MA : Springer US, 1994. http://dx.doi.org/10.1007/978-1-4615-2988-0_3.

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Yang, Shi-zhen, Wei Lin, Yi-ding Huang, You-min Feng et Ching-I. Niu. « Insulin analogs with alterations at A8-10 ». Dans Peptide Chemistry 1992, 409–12. Dordrecht : Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1474-5_121.

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Beals, John M. « Insulin Analogs - Improving the Therapy of Diabetes ». Dans Successful Drug Discovery, 35–60. Weinheim, Germany : Wiley-VCH Verlag GmbH & Co. KGaA, 2015. http://dx.doi.org/10.1002/9783527678433.ch3.

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Videnov, G., K. Büttner, M. Casaretto, J. Föhles, H. G. Gattner, S. Stoev, K. C. Goyal et D. Brandenburg. « Towards the synthesis of an A7-B7-dicarba insulin analogue ». Dans Peptides 1990, 232–33. Dordrecht : Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3034-9_97.

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Fan, L., L. A. Alter, R. M. Ellis, A. M. Korbas, G. S. Brooke et R. E. Chance. « Chymotrypsin-catalyzed semisynthesis : An alternative approach for synthesis of insulin analogs ». Dans Peptides, 549–50. Dordrecht : Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_213.

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Long, H. B., J. C. Baker, R. M. Belagaje, R. D. DiMarchi, B. H. Frank, L. K. Green, J. A. Hoffmann et al. « Human insulin analogs with rapid onset and short duration of action ». Dans Peptides, 88–90. Dordrecht : Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_27.

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Actes de conférences sur le sujet "Analoghi insulina"

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Zedelmair, Michael M., et Abhijit Mukherjee. « Numerical Simulation of Insulin Depot Formation in Subcutaneous Tissue ». Dans ASME 2016 Fluids Engineering Division Summer Meeting collocated with the ASME 2016 Heat Transfer Summer Conference and the ASME 2016 14th International Conference on Nanochannels, Microchannels, and Minichannels. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/fedsm2016-7719.

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In this study a numerical model of the insulin depot formation and absorption in the subcutaneous adipose tissue is developed using the commercial Computational Fluid Dynamics (CFD) software ANSYS Fluent. A better understanding of these mechanisms can be helpful in the development of new devices and cannula geometries as well as predicting the concentration of insulin in the blood. The injection method considered in this simulation is by the use of an insulin pump using a rapid acting U100 insulin analogue. The insulin is injected into the subcutaneous tissue in the abdominal region. The main composition of the subcutaneous tissue is blood vessels and adipose cells surrounded by interstitial fluid. The numerical simulation is conducted in a 2D-axisymmetric domain where the tissue is modeled as a fluid saturated porous media. Due to the presence of channel formation in lateral direction in the tissue, an anisotropic approach to define the permeability is studied having an impact on the viscous resistance to the flow. This configuration is resulting in a rather disk shaped depot following recent experimental findings. The depot formation is analyzed running Bolus injections ranging from 5–15 Units of insulin corresponding to 50–150μl. The depot formation model has been extended implementing the process of absorption of insulin from the depot to be able to run the simulation over longer timeframes where absorption starts playing an important role.
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Teupe, B. « Late revenge of analogue insulins among T1D-patients ? » Dans Diabetes Kongress 2018 – 53. Jahrestagung der DDG. Georg Thieme Verlag KG, 2018. http://dx.doi.org/10.1055/s-0038-1641851.

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Pagkalos, Ilias, Pau Herrero et Pantelis Georgiou. « An analogue implementation of the beta cell insulin release model ». Dans 2013 IEEE International Symposium on Circuits and Systems (ISCAS). IEEE, 2013. http://dx.doi.org/10.1109/iscas.2013.6572384.

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Kobylska, Ewa, Marcin Drozd, Małgorzata Żmieńko et Michał Chudy. « Studies on Recombinant Insulin Analogs Interactions with Partner Cell Membrane Receptors Using the SPR Technique ». Dans I3S2022Warsaw. Basel Switzerland : MDPI, 2022. http://dx.doi.org/10.3390/engproc2022021022.

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Ježek, Jan, Jiří Velek, Vlasta Velková, Lenka Klasová, Jana Barthová, Karel Ubik, Václav Kašička et al. « Preparation and characterization of analogs of tetrapeptide B23-B26 and octapeptide B23-B30 of human insulin ». Dans VIth Conference Biologically Active Peptides. Prague : Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 1999. http://dx.doi.org/10.1135/css199903082.

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Klasová, Lenka, Karel Huml, Jana Barthová, Karel Ubik, Václav Kašička, Josef Škarda, Linda Hauzerová et al. « Semisynthetic preparation of human insulin analogs containing N-methylated B24-B25 or B25-B26 peptide bonds ». Dans VIth Conference Biologically Active Peptides. Prague : Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 1999. http://dx.doi.org/10.1135/css199903085.

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King, A., C. Arnaud, G. Vial, E. Billoir, B. Ozcan, E. Belaidi, C. O'Donnell et S. Ryan. « The effect of the GLP-1 analogue Liraglutide on intermittent hypoxia-induced systemic insulin resistance in vivo ». Dans ERS International Congress 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/13993003.congress-2022.2182.

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Škarda, Josef, Lucie Buriánová, Monika Mrazíková, Lenka Klasová, Jana Barthová, Tomislav Barth et Karel Ubik. « New semisynthetic analogs of human insulin and their interaction with IGF-I receptors in mouse mammary explants ». Dans VIIth Conference Biologically Active Peptides. Prague : Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2001. http://dx.doi.org/10.1135/css200104060.

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