Emma Ahlqvist

Hjelt grant holder 2016, Lund university

Dissection of the molecular mechanisms of glucose-stimulated hormone secretion during OGTT using GWAS

The hormones secreted in response to an oral glucose tolerance test (OGTT) are central players in regulating blood glucose. Insulin and glucagon are secreted in response to high and low glucose respectively and regulate glucose uptake and release in peripheral tissues, keeping blood glucose at healthy levels. The two incretin hormones GIP and GLP-1 are secreted by cells in the intestine in response to nutrient stimulation and have insulin-stimulating capacity as well as numerous other functions in the metabolic and cardiovascular systems. By using genome-wide association studies (GWAS) we have identified a number of genetic variants that affect the levels of GIP, GLP-1 and glucagon in blood, both in the fasting state and after an oral glucose tolerance test. The aim of this project is to identify the genes that mediate the effect of the genetic variants and to functionally characterize the involved cellular mechanisms. We will do this by genetic analysis of related traits in different human cohorts, by studying the expression of candidate genes in relevant tissues and by exploring the function of candidate genes in cell lines, animal models and human tissue. This way, we hope to identify genes and cellular pathways involved in hormone secretion and inactivation that are potential therapeutic targets for treatment of type 2 diabetes and obesity.

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