Glucose and leptin induce apoptosis in human β‐ cells and impair glucose‐stimulated insulin secretion through activation of c‐Jun N‐terminal kinases

• DOI: 10.1096/fj.07-101824
• Publication Date: 2008-02-09T02:40:55Z
• Authors: Kathrin Maedler; Fabienne T. Schul...; Christelle Bielman; Thierry Berney; Christophe Bonny; Marc Prentki; Marc Y. Donath; Raphael Roduit
• Keywords: c-jun; Pancreatic Islets

c-Jun N-terminal kinases (SAPK/JNKs) are activated by inflammatory cytokines, and JNK signaling is involved in insulin resistance beta-cell secretory function survival.Chronic high glucose concentrations leptin induce interleukin-1beta (IL-1beta) secretion from pancreatic islets, an event that possibly causal promoting dysfunction death.The present study provides evidence chronically elevated of apoptosis through activation the pathway human islets insulinoma (INS 832/13) cells.JNK inhibition dominant inhibitor JNK-binding domain IB1/JIP-1 (JNKi) reduced activity induced glucose.Exposure to leads a decrease glucose-induced secretion, which was partly restored JNKi.We detected interplay between cascade caspase 1/IL-1beta-converting enzyme islets.The 1 gene, contains potential activating protein-1 binding site, up-regulated sections isolated type 2 diabetic patients.Similarly, cultured exposed glucose-and leptin-induced prevented this up-regulation.Therefore, may protect beta-cells deleterious effects diabetes.