Skip to main content

Jacobson Lab

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

AUTHORS

Zhu LLu , Almaça J Joana , Dadi PK Prasanna K , Hong H Hao , Sakamoto W Wataru , Rossi M Mario , Lee RJ Regina J , Vierra NC Nicholas C , Lu H Huiyan , Cui Y Yinghong , McMillin SM Sara M , Perry NA Nicole A , Gurevich VV Vsevolod V , Lee A Amy , Kuo B Bryan , Leapman RD Richard D , Matschinsky FM Franz M , Doliba NM Nicolai M , Urs NM Nikhil M , Caron MG Marc G , Jacobson DA David A , Caicedo A Alejandro , Wess J Jürgen . Nature communications. 2017 2 1; 8(). 14295

ABSTRACT

β-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 β-arrestin-2 gene, barr2, in β-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 β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function.

β-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 β-arrestin-2 gene, barr2, in β-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 β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function.