, a bio/informatics shared resource is still "open for business" - Visit the CDS website

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

Zhu L, Almaça J, Dadi PK, Hong H, Sakamoto W, Rossi M, Lee RJ, Vierra NC, Lu H, Cui Y, McMillin SM, Perry NA, Gurevich VV, Lee A, Kuo B, Leapman RD, Matschinsky FM, Doliba NM, Urs NM, Caron MG, Jacobson DA, Caicedo A, Wess J
Nat Commun. 2017 8: 14295

PMID: 28145434 · PMCID: PMC5296650 · DOI:10.1038/ncomms14295

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.

MeSH Terms (16)

Animals beta-Arrestin 2 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Cell Line Cell Line, Tumor Diet, High-Fat Gene Expression Humans Insulin Insulin-Secreting Cells Insulin Secretion Islets of Langerhans Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Signal Transduction

Connections (2)

This publication is referenced by other Labnodes entities: