Dr. Annika Bagge

Hjelt grant holder 2014, Lund university

Does Micu2 control insulin secretion? – A role in health and disease

Dr. Annika Bagge, “Does Micu2 control insulin secretion? – A role in health and disease” (€ 25 000):
In Type 2 diabetes glucose-stimulated insulin secretion (GSIS) is impaired. In β-cells, GSIS is tightly coupled to the metabolism of glucose, which ultimately results in a rise in intra-cellular calcium (Ca2+) levels activating the insulin-secretion-mechanism. Ca2+ is also taken up by the mitochondria through the Mitochondrial Calcium Uniporter complex (MCU-complex). This Ca2+-uptake as well as the MCU-complex have been shown to be important for GSIS, but the function of mitochondrial Ca2+ is still not fully understood. Micu2 was recently identified in mouse liver as a subunit of the MCU-complex functioning as a gate-keeper for mitochondrial Ca2+-uptake. However, The fact that a genetic variation in the Micu2 gene affects beta-cell function and insulin secretion in humans suggests that Micu2 has an important function in β-cells. The project aims at elucidating the function of Micu2 in pancreatic β-cells by studying the metabolic effects of removing and/or adding Micu2 in cultured β-cells. In addition, we will examine the pathophysiological role of Micu2 in mice in which Micu2 is genetically deleted. The project should lead to better understanding of the role of the MCU-complex as well as Ca2+ signaling in β-cells, and ultimately lead to improved understanding, prevention and treatment of T2D.

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