scholarly journals Glucagon-Like Peptide-1 Triggers Protective Pathways in Pancreatic Beta-Cells Exposed to Glycated Serum

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
Arianna Durante ◽  
Alessio Nencioni ◽  
François Mach ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Redox Balance ◽  
Insulin Gene ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pancreatic Beta Cell Function

Advanced glycation end products (AGEs) might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates glucose homeostasis, might counteract the harmful effects of AGEs on the beta cells in culture. The aim of this study was to identify the intracellular mechanisms underlying GLP-1-mediated protection from AGE-induced detrimental activities in pancreatic beta cells. HIT-T15 cells were cultured for 5 days with glycated serum (GS, consisting in a pool of AGEs), in the presence or absence of 10 nmol/L GLP-1. After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. Then, we investigated proinsulin production. The results showed that GS increased oxidative stress, reduced protein expression of all investigated factors through proteasome activation, and decreased proinsulin content. Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. Coincubation with GLP-1 reversed these GS-mediated detrimental effects. In conclusion, GLP-1, protecting cells against oxidants, triggers protective intercellular pathways in HIT-T15 cells exposed to GS.

Membrane and intracellular effects of adenosine in mouse pancreatic beta-cells

1989 ◽  
Vol 257 (4) ◽  
pp. E473-E478 ◽  
Author(s):  
G. Bertrand ◽  
P. Petit ◽  
M. Bozem ◽  
J. C. Henquin
Keyword(s):  
Electrical Activity ◽  
Beta Cells ◽  
Insulin Release ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Islet Cells ◽  
Pancreatic Beta Cell ◽  
Nucleoside Transport ◽  
High Concentration ◽  
Pancreatic Beta Cell Function

Mouse islets were used to study the effects of adenosine and its stable analogue L-N6-phenylisopropyladenosine (L-PIA) on pancreatic beta-cell function. At a high concentration (500 microM), adenosine augmented glucose-induced electrical activity in beta-cells and potentiated insulin release. These effects were prevented by the inhibitor of nucleoside transport nitrobenzylthioguanosine. They probably result from the metabolism of adenosine by beta-cells. At a lower concentration (50 microM), adenosine caused a small and transient inhibition of glucose-induced electrical activity and insulin release. L-PIA (10 microM) slightly and transiently inhibited insulin release, 45Ca efflux and 86Rb efflux from islet cells, and decreased electrical activity in beta-cells. When adenylate cyclase was stimulated by forskolin in the presence of 15 mM glucose, insulin release was strongly augmented. Under these conditions, L-PIA and adenosine (with nitrobenzylthioguanosine) caused a sustained inhibition. No such inhibition was observed when insulin release was potentiated by dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). These data are consistent with the existence of A1 purinergic receptors on mouse beta-cells. They could mainly serve to attenuate the amplification of insulin release brought about by agents acting via cAMP.

scholarly journals Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Puddu ◽  
Roberta Sanguineti ◽  
François Mach ◽  
Franco Dallegri ◽  
Giorgio Luciano Viviani ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Molecular Pathways ◽  
Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

Prenatal androgen excess impairs beta cell function by decreased Sirtuin3 expression

2021 ◽  
Author(s):  
Yu Zhou ◽  
Min Gong ◽  
Yingfei Lu ◽  
Jianquan Chen ◽  
Rong Ju
Keyword(s):  
Oxidative Stress ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Female Offspring ◽  
Sirtuin 3 ◽  
Prenatal Testosterone ◽  
Pancreatic Beta Cell Function ◽  
Prenatal Androgen

Prenatal androgen exposure induces metabolic disorders in female offspring. However, the long-term effect of maternal testosterone excess on glucose metabolism, especially on pancreatic beta cell function, is rarely investigated. Our current study mainly focused on the effects of prenatal testosterone exposure on glucose metabolism and pancreatic beta cell function in aged female offspring. By using maternal mice and their female offspring as animal models, we found that prenatal androgen treatment induced obesity and glucose intolerance in aged offspring. These influences were accompanied by decreased fasting serum insulin concentration, elevated serum triglyceride and testosterone concentrations. Glucose stimulated insulin secretion in pancreatic beta cells of aged female offspring was also affected by prenatal testosterone exposure. We further confirmed that increased serum testosterone contributed to down regulation of Sirtuin 3 expression, activated oxidative stress and impaired pancreatic beta cell function in aged female offspring. Moreover, over-expression of Sirtuin 3 in islets isolated from female offspring treated with prenatal testosterone normalized the oxidative stress level, restored cyclic adenosine monophosphate and adenosine triphosphate generation, which finally improved glucose stimulated insulin secretion in beta cells. Taken together, these results demonstrated that prenatal testosterone exposure caused metabolic disturbance in aged female offspring via suppression of Sirtuin 3 expression and activation of oxidative stress in pancreatic beta cells.

scholarly journals Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37)

Nature ◽  
1993 ◽  
Vol 361 (6410) ◽  
pp. 362-365 ◽  
Author(s):  
George G. Holz IV ◽  
Willem M. Kiihtreiber ◽  
Joel F. Habener
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1: a major regulator of pancreatic beta-cell function

2000 ◽  
pp. 717-725 ◽  
Author(s):  
R Perfetti ◽  
P Merkel
Keyword(s):  
Beta Cell ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Glucagon Secretion ◽  
Insulin Biosynthesis ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone synthesized by post-translational processing in intestinal L-cells, and it is released in response to food ingestion. GLP-1 stimulates insulin secretion during hyperglycemia, suppresses glucagon secretion, stimulates (pro)-insulin biosynthesis and decreases the rate of gastric emptying and acid secretion. GLP-1 has also been shown to have a pro-satiety effect. In addition, it has been demonstrated that a long-term infusion with GLP-1, or exendin-4, a long-acting analog of human GLP-1, increases beta-cell mass in rats. In conclusion, GLP-1 appears to regulate plasma glucose levels via various and independent mechanisms. GLP-1 is an excellent candidate option for the treatment of patients with type 2 diabetes mellitus.

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