Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B

The gut hormone glucagon-like peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present stud...

Full description

Saved in:
Bibliographic Details
Published in:Diabetologia 2005-07, Vol.48 (7), p.1339
Main Authors: Li, L, El-Kholy, W, Rhodes, C J, Brubaker, P L
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Caspase 3
Caspases - metabolism
Cell Division - drug effects
Cell growth
Cell Line
Cell Survival - drug effects
Cytokines
Cytokines - pharmacology
Diabetes
Fatty acids
Glucagon
Glucagon-Like Peptide-1 Receptor
Islets of Langerhans - cytology
Islets of Langerhans - drug effects
Islets of Langerhans - immunology
Islets of Langerhans - pathology
Kinases
Male
Necrosis
Nitric oxide
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Peptides
Peptides - pharmacology
Protein-Serine-Threonine Kinases - physiology
Proteins
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-akt
Rats
Rats, Wistar
Receptors, Glucagon - agonists
Receptors, Glucagon - physiology
Venoms - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The gut hormone glucagon-like peptide-1 (GLP-1) decreases beta cell apoptosis in a protein kinase B (PKB)-dependent fashion, and increases islet cell mass and function in vivo. In contrast, cytokines induce beta cell apoptosis, leading to decreased islet mass and type 1 diabetes. In the present study we used rat INS-1E beta cells and primary rat islet cells to examine the potential role of PKB as a mediator of the effect of GLP-1 on cytokine-induced apoptosis. Cell viability was determined by MTT assay, and apoptosis and necrosis by Hoechst 33342-propidium iodide staining. Immunoblot analysis was used to detect changes in protein expression, including active (phosphorylated) and total PKB, phosphorylated and total glycogen synthase kinase-3beta, activated caspase-3 and inducible nitric oxide synthase. Reactive oxygen species were determined by 1,7-dichlorofluorescein (DCF) analysis, and mutant forms of PKB were introduced into cells using adenoviral vectors. Incubation of INS-1E cells with cytokines (IL-1beta, TNF-alpha and interferon-gamma; 10-50 ng/ml) for 18 h significantly decreased cell viability (by 44%, p
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-005-1787-2