Incretin-based therapy and pancreatic beta cells

Chon, Suk; Riveline, Jean‐Pierre; Blondeau, B.; Gautier, J.-F.

doi:10.1016/j.diabet.2014.05.003

Cited by 9 publications

(10 citation statements)

References 102 publications

(126 reference statements)

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“…Thiazolidinediones have been demonstrated to have a direct adrenocorticotropic hormone (ACTH)-lowering effect on corticotrophinomas in vitro, but no convincing results arose from clinical trials on patients with CD (47). GLP1 analogues and dipeptidyl peptidase four inhibitors could be helpful in the management of GC-induced diabetes, increasing glucose dependent insulin secretion and reducing glucagon secretion as well as having positive effects on b-cell mass and function, appetite, adipocyte modulation, fat distribution, hyperlipidaemia, heart and bone (48,49). Incretin-based medications have been suggested for the management of pasireotide-induced hyperglycaemia, since somatostatin receptor inhibition leads to reduced secretion of GLP1, glucose-dependent insulinotropic polypeptide and insulin (50,51).…”

Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

145

121

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Section: Gcs and Glucose Metabolismmentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

145

121

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“…Clinical studies have previously shown that exendin-4 could dose-dependently decrease the fasting and postprandial blood glucose, lower the HbA1c level, restore the blunted first phase insulin secretion, enhance the second phase insulin secretion and inhibit glucagon secretion. 12) Chronic treatment with GW002 was assessed in diabetic db/db and KKAy mice by subcutaneous injection once daily. The results showed that chronic treatment with GW002 could significantly control the non-fasting blood glucose and HbA1c levels, increase insulin secretion and suppress glucagon secretion therefore improving the imbalance of insulin and glucagon in controlling glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

A Human Glucagon-Like Peptide-1-albumin Recombinant Protein with Prolonged Hypoglycemic Effect Provides Efficient and Beneficial Control of Glucose Metabolism in Diabetic Mice

Yang

Hou

et al. 2017

Biological & Pharmaceutical Bulletin

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GW002 is a recombinant protein engineered by fusing the C-terminal region of human glucagon-like peptide-1 (GLP-1) to the N-terminal region of human serum albumin (HSA) with a peptide linker. This study aims to evaluate its anti-diabetic effects both in vitro and in vivo. The GLP-1 receptor-dependent luciferase reporter plasmid was transiently transfected in NIT-1 cells to calculate the half-maximal concentration (EC) for GLP-1 receptor activation, and normal ICR mice and diabetic KKAy mice were acutely injected with GW002 (1, 3, 9 mg/kg) subcutaneously to evaluate the hypoglycemic action, while the diabetic KKAy and db/db mice were treated with GW002 once daily for 7 weeks to evaluate the effects on glucose metabolism. The results showed that GW002 activated GLP-1 receptor in NIT-1 cells with higher EC versus exendin-4 (46.7 vs. 7.89 nM), and single subcutaneous injection of GW002 at doses of 1, 3 and 9 mg/kg efficiently restrained the glycemia variation after oral glucose loading in ICR mice for at least 4 d, as well as reducing the non-fasting blood glucose in KKAy mice for about 2 d, while repeated injections of GW002 significantly improved abnormal glycaemia, hemoglobin (Hb)A1c levels, oral glucose intolerance and β-cell function in diabetic db/db mice. These results suggested that GW002 showed prolonged hypoglycemic action by activating its cognate receptor and provided efficient control of glucose metabolism. Thus GW002 may be a potential treatment for the management of type 2 diabetes.

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“…Multiple factors, including glucotoxicity, lipotoxicity, inflammation, cytokines, islet amyloid deposits, autoimmunity, incretin defects, and insulin resistance, have been suggested to be key pathophysiological features of defective β-cells in patients with T2DM ( Fig. 1 ) [ 4 ].…”

Section: Pancreatic β-Cell Function and Mass In Type 2 Diabetes Mellimentioning

confidence: 99%

“…Here, we provide an update on our previous review of incretin hormones and their association with pancreatic β-cell function and mass in diabetes mellitus [ 4 ] based on recent experimental and clinical findings.…”

Section: Introductionmentioning

confidence: 99%

An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

Chon

Gautier

2016

Diabetes Metab J

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Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.

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Incretin-based therapy and pancreatic beta cells

Cited by 9 publications

References 102 publications

Metabolic comorbidities in Cushing's syndrome

Metabolic comorbidities in Cushing's syndrome

A Human Glucagon-Like Peptide-1-albumin Recombinant Protein with Prolonged Hypoglycemic Effect Provides Efficient and Beneficial Control of Glucose Metabolism in Diabetic Mice

An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

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