Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity

• Published in: Journal of Diabetes Research Vol. 2016; no. 2016; pp. 1 - 9
• Main Authors: Abderrahmani, Amar, Waeber, Gérard, Hai, Tsonwin, Zmuda, Erik, Plaisance, Valérie, Ezanno, Hélène, Pawlowski, Valérie, Ferdaoussi, Mourad, Brajkovic, Saška, Annicotte, Jean-Sébastien
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antibodies; Apoptosis; Cell Line; Cell Survival - drug effects; Cell Survival - genetics; Cytokines; Dextrose; Diabetes; Fatty acids; Gene expression; Genetic aspects; Glucose; Infrared imaging systems; Insulin; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Kinases; Male; Palmitic Acid - pharmacology; Protein kinases; Proteins; Rats; Rats, Sprague-Dawley; RNA; RNA, Messenger - metabolism; Type 2 diabetes; St Louis Missouri
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2016/9158562

Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate. Chronic exposure of MIN6 and isolated rat islets cells to palmitate led to reduction of the IB1 mRNA and protein content. Diminution of IB1 mRNA and protein level relied on the inducible cAMP early repressor activity and proteasome-mediated degradation, respectively. Suppression of IB1 level mimicked the harmful effects of palmitate on the beta cell survival and GSIS. Conversely, ectopic expression of IB1 counteracted the deleterious effects of palmitate on the beta cell survival and insulin secretion. These findings highlight the importance in preserving the IB1 content for protecting beta cell against lipotoxicity in diabetes.