?-arrestin-2 is an essential regulator of pancreatic ?-cell function under physiological and pathophysiological conditions.

ABSTRACT: ?-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the ?-arrestin-2 gene, barr2, in ?-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in ?-arrestin-2 (barr2) deficient ?-cells. In human ?-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in ?-cells. Importantly, overexpression of barr2 in ?-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of ?-cell function, which may serve as a new target to improve ?-cell function.

SUBMITTER: Zhu L 

PROVIDER: S-EPMC5296650 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature