Enhancing Insulin Secretion by the Novel Adipokine Glypican-4

• Applicant: Dr. Siegfried Ussar
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 292470091

Driven by the ever-growing availability of highly caloric food options and a sedentary lifestyle, obesity is a global challenge affecting hundreds of millions of people worldwide. Eventually, excessive body fat, resulting in dysfunctional adipose tissue, leads to local and systemic insulin resistance. To compensate this peripheral insulin resistance, pancreatic beta-cells respond with increased insulin secretion to maintain glucose homeostasis. The inability to do so results in deregulated glucose homeostasis and ultimately type 2 diabetes. Thus, detailed understanding of the regulatory networks supporting beta-cell function is essential to limit the detrimental consequences of obesity and adipose tissue dysfunction. We have previously reported that the cell surface proteoglycan glypican-4 can bind to and enhance insulin receptor activation. Moreover, our data show that glypican-4 is released from adipocytes into the circulation and that its serum levels correlate with metrics of body fat and insulin resistance in mice and men. Based upon our preliminary data, the key objective of this project is to define the role of the novel adipokine glypican-4 in the insulin receptor mediated insulin secretion from beta-cells. Furthermore, we will elucidate the regulatory network underlying the release of glypican-4 from the adipocyte cell surface into the circulation. Overall this project will deepen our understanding of the regulatory networks supporting beta-cell function to limit the detrimental consequences of obesity.

• DFG Programme: Research Grants