Gender specific effects of Nr4a1 on functional β‐cell mass

Abstract

Nuclear hormone receptor4a1 (Nr4a1) plays a critical role in β‐cell replication, function, and survival. β‐cell replication is tightly regulated, most β‐cells in the body are formed during development and shortly after birth. Nr4a1 full body knock‐out mice have a 50% reduction in total β‐cell area. Nr4a1 knock down INS‐1 832/13 β‐cells have decreased mitochondrial respiration, glucose stimulated insulin secretion and cellular proliferation. Fatty acids regulate Nr4a1 activity and expression. Here we present the effects of β‐cell specific Nr4a1 deletion on mice exposed to a high fat or normal chow diet beginning at 3‐months of age. Our data demonstrate that loss of β‐cell Nr4a1 results in improved non‐fasting blood glucose and glucose tolerance in male mice fed a high fat diet for 4 months. Interestingly, female mice deficient for Nr4a1 have impaired glucose tolerance as early as 1 months of high fat feeding. Furthermore, we show data regarding β‐cell mass and glucose stimulated insulin secretion. These data demonstrate a clear gender bias in Nr4a1 function in the β‐cell.Support or Funding InformationADA 1‐17‐IBS‐101 to JSTThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.