Speaker

ALAN D. ATTİE

Professor, Biochemistry
University of Wisconsin

Alan Attie has worked on metabolic aspects of cardiovascular disease since 1976. He has worked on lipoprotein metabolism, cholesterol transport, and in more recent years, the genetics of diabetes. His laboratory combines metabolic research with current approaches to genetics and genomics. His laboratory has extensive experience with microarray analysis and integration of high-volume data from The current projects are aimed at understanding -cell proliferation, insulin secretion, insulin action, and hepatic steatosis.

Abstract

The Genetic Architecture of Insulin Secretion
Alan D. Attie
University of Wisconsin-Madison

Most of the genetic contribution to the risk of type 2 diabetes comes from variation in -cell mass and function. Insulin secretion requires nutrient sensing and metabolism, secondary signaling pathways, and the biogenesis and trafficking of insulin granules. Using two different genetic screens, we have identified loci responsible for variation in insulin secretion. Our first screen was an F2 intercross between a diabetes-resistant and diabetes-susceptible mouse strain. We identified Tomosyn2 and Sorcs1 as genes involved in insulin secretion. Tomosyn 2 is an inhibitor of insulin secretion. Sorcs1, a member of the vps10 protein family, plays a role in the biogenesis of insulin granules. At present, we are screening an outcross stock derived from 8 inbred mouse strain, the Diversity Outcross (DO). This outcross contains an extraordinary level of genetic and phenotypic diversity. We isolated islets from each mouse and measured insulin secretion in response to 7 secretagogues. We have identified~40 loci that influence insulin secretion and islet number. In addition, we have mapped host loci that affect the microbiome composition as well as fecal bile acids. Our loci are highly correlated with genetic hits in humans. The alleles from the wild-derived strains are the main contributors to the genetic associations and are the ones that most closely resemble the human associations.

Symposium Faculty

ALAN D. ATTIE

Professor, Biochemistry
University of Wisconsin

LAURIE H. GLIMCHER

Professor, Dean of Cornell Medical School

ROBERT FARESE

Professor, Genetics and Complex Diseases
Harvard T.H. Chan School of Public Health

GÖKHAN HOTAMIŞLIGİL

Professor, Genetics and Metabolism and Nutrition
Harvard University

BRIAN KOBILKA

Professor, Department of Molecular and Cellular Physiology
Stanford University

SUSANNE MANDRUP

Professor, Biochemistry and Molecular Biology
University of Southern Denmark

EMILIE MARCUS

CEO of Cell Press and Editor of Cell

RUSLAN MEDZHITOV

David W. Wallace Professor of Immunobiology; Investigator, Howard Hughes Medical Institute, Yale University, HHMI

IRA TABAS

Professor, Anatomy Cell Biology
Columbia University

PETER TONTONOZ

Professor, Pathology and Laboratory Medicine
University of California Los Angeles

DENİZ ATASOY

Assistant Professor, Physiology, School of Medicine
İstanbul Medipol University

EBRU ERBAY

Assistant Professor, Molecular Biology and Genetics
Bilkent University

KIVANÇ BİRSOY

Assistant Professor, Molecular Biology and Genetics
Rockefeller University

LALE OZCAN

Assistant Professor, Department of Medicine
Columbia University Medical Center