Cholesterol metabolism and insulin secretion in islets from hypercholesterolemic mice: possible participate of endoplasmic reticulum stress

• Grant number: 12/21290-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 01, 2013
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Jane Cristina de Souza Sporkens
• Supervisor: Ira Abram Tabas
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Columbia University in the City of New York, United States
• Associated to the scholarship: 11/23370-2 - Cholesterol metabolism and insulin containing granule movement in islets from hypercholesterolemic mice: Possible participate of Endoplasmic Reticulum Stress, BP.PD

Abstract

Changes in cellular cholesterol levels may contribute to B cell dysfunction. Islets from LDL receptor knockout mice (LDLR-/-) possess higher cholesterol content, showing impaired calcium handling, lower expression of proteins that promotes granule extrusion and lower insulin secretion than wild type (WT) mice. The endogenous cholesterol synthesis occurs through a series of enzymatic reactions known as the Mevalonate pathway. When activated, this pathway generates intermediary that promote post-translational modifications in proteins involved in granule extrusion process. Synthesis and accumulation of cholesterol in the endoplasmic reticulum (ER) are associated with the development of ER stress, resulting in a reduction of B cell mass and function. Based on this, the aim of this project is to evaluate whether the excess of cholesterol leads to development of endoplasmic reticulum stress triggering the Unfolded Protein Response (UPR). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OZCAN, LALE; GHORPADE, DEVRAM S.; ZHENG, ZE; DE SOUZA, JANE CRISTINA; CHEN, KE; BESSLER, MARC; BAGLOO, MELISSA; SCHROPE, BETH; PESTELL, RICHARD; TABAS, IRA. Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance. CELL REPORTS, v. 15, n. 10, p. 2214-2225, JUN 7 2016. (12/21290-4)

OZCAN, LALE; DE SOUZA, JANE CRISTINA; HARARI, ALP AVI; BACKS, JOHANNES; OLSON, ERIC N.; TABAS, IRA. Activation of Calcium/Calmodulin- Dependent Protein Kinase II in Obesity Mediates Suppression of Hepatic Insulin Signaling. Cell Metabolism, v. 18, n. 6, p. 803-815, DEC 3 2013. (12/21290-4)