Exendin-4 protects murine pancreatic β-cells from free fatty acid-induced apoptosis through PI-3K signaling.
BACKGROUND
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the L-cells of the distal intestine that has proliferative and anti-apoptotic actions on the β-cell.


METHODS
In this study, exendin-4, a long-acting GLP-1 receptor agonist, was studied as a novel agent to suppress apoptosis in pancreatic β-cells and to protect against free fatty acid (FFA)-induced cytotoxicity.


RESULTS
Exendin-4 significantly reduced the percentage of cells that underwent apoptosis when β-cells were exposed to FFA. Exendin-4 increased the levels of P-Akt and Bcl-2 proteins in FFA-induced β-cells, and this effect was blocked by Wortmannin.


CONCLUSIONS
These results suggest that phosphoinositide-3 kinase signaling is involved in the modulation of β-cell apoptosis which is induced by exendin-4. Taken together, our findings provide a new mechanism for the modulation of exendin-4 in the pathological processes underlying FFA-induced diabetes mellitus.
Department of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
Liang
L
Liu
Yanping
Y
Wang
Linxi
L
Wang
Yichuan
Y
Lin
Xiaohong
X
Liu
Xiaoying
X
Liu
Libin
L
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D000077270:Exenatide; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000819:agonists; D015398:Signal Transduction / Q000502:physiology*; D014688:Venoms / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
C494827:Bax protein, mouse; D005230:Fatty Acids, Nonesterified; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D018027:Receptors, Glucagon; D014688:Venoms; D051028:bcl-2-Associated X Protein; D000077270:Exenatide; D019869:Phosphatidylinositol 3-Kinases