[iBET – ITQB NOVA] Small molecule modulation of lipid metabolism protect β cells against Lipotoxic induced dysfunction

iBET – ITQB NOVA Seminar

Title: Small molecule modulation of lipid metabolism protect β cells against Lipotoxic induced dysfunction

Speaker: El Hadji M Dioum

Affiliation: Nestlé Institute of Health Sciences, Lausanne Switzerland

Host: Regina Menezes

Abstract:

Glucolipotoxicity, is one of the major factors linked to progressive loss of pancreatic β cell function and survival in type 2 diabetes (T2D). The β cell has an intrinsic capacity to combat cytotoxic stress by regulating genes involved in specific pro-survival and metabolic processes. Understanding and modulating the response of β cells in glucolipotoxic conditions is important in the prevention and cure of T2D. Here we use the small molecule inducer of β cell differentiation (Isx9) to mitigate the impairment induced by chronic palmitate in β cells. Glucose blindness, reduced cell survival and insulin secretion induced by palmitate is reversed by Isx9 in INS1E cells through upregulation Glut2 and mitochondrial function. Microarray IPA data analysis of rat islets treated with Isx9 indicate the modulation of pathways involved in FA metabolism and detoxification via PPARα/RXR activation. The expression of a major gene involved in fatty acid β-oxidation (Acaa2) induced by Isx9 and palmitate, play a significant role in these processes. In an obesity induced T2D mouse model (db/db) Isx9 significantly improved glucose tolerance and insulin secretion. In conclusion, Isx9 can be used to pharmacologically activate genes and