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

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.

Dual glucagon recognition by pancreatic beta-cells via glucagon and glucagon-like peptide 1 receptors

Diabetes ◽  
1998 ◽  
Vol 47 (1) ◽  
pp. 66-72 ◽  
Author(s):  
K. Moens ◽  
D. Flamez ◽  
C. Van Schravendijk ◽  
Z. Ling ◽  
D. Pipeleers ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Agonist binding affinity determines palmitoylation of the glucagon-like peptide-1 receptor and its functional interaction with plasma membrane nanodomains in pancreatic beta cells

2018 ◽  
Author(s):  
Teresa Buenaventura ◽  
William E Laughlin ◽  
Stavroula Bitsi ◽  
Thomas Burgoyne ◽  
Zekun Lyu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Binding Affinity ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cluster Formation ◽  
Acyl Chain ◽  
Dependent Manner ◽  
Agonist Binding ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The glucagon-like peptide-1 receptor (GLP-1R), a key pharmacological target in type 2 diabetes and obesity, is known to undergo palmitoylation by covalent ligation of an acyl chain to cysteine 438 in its carboxyl-terminal tail. Work with other GPCRs indicates that palmitoylation can be dynamically regulated to allow receptors to partition into plasma membrane nanodomains that act as signaling hotspots. Here, we demonstrate that the palmitoylated state of the GLP-1R is increased by agonist binding, leading to its segregation and clustering into plasma membrane signaling nanodomains before undergoing internalization in a clathrin-dependent manner. Both GLP-1R signaling and trafficking are modulated by strategies targeting nanodomain segregation and cluster formation, including depletion of cholesterol or expression of a palmitoylation-defective GLP-1R mutant. Differences in receptor binding affinity exhibited by biased GLP-1R agonists, and modulation of binding kinetics with the positive allosteric modulator BETP, influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. Downstream effects on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable.

Sign in / Sign up

Export Citation Format

Share Document