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.
| Original language | English (US) |
|---|---|
| Article number | 14295 |
| Journal | Nature Communications |
| Volume | 8 |
| DOIs | |
| State | Published - Feb 1 2017 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
β-Arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions. / Zhu, Lu; Almaca, Joana; Dadi, Prasanna K.; Hong, Hao; Sakamoto, Wataru; Rossi, Mario; Lee, Regina J.; Vierra, Nicholas C.; Lu, Huiyan; Cui, Yinghong; McMillin, Sara M.; Perry, Nicole A.; Gurevich, Vsevolod V.; Lee, Amy; Kuo, Bryan; Leapman, Richard D.; Matschinsky, Franz M.; Doliba, Nicolai M.; Urs, Nikhil M.; Caron, Marc G.; Jacobson, David A.; Caicedo-Vierkant, Diego A; Wess, Jürgen.
In: Nature Communications, Vol. 8, 14295, 01.02.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β-Arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions
AU - Zhu, Lu
AU - Almaca, Joana
AU - Dadi, Prasanna K.
AU - Hong, Hao
AU - Sakamoto, Wataru
AU - Rossi, Mario
AU - Lee, Regina J.
AU - Vierra, Nicholas C.
AU - Lu, Huiyan
AU - Cui, Yinghong
AU - McMillin, Sara M.
AU - Perry, Nicole A.
AU - Gurevich, Vsevolod V.
AU - Lee, Amy
AU - Kuo, Bryan
AU - Leapman, Richard D.
AU - Matschinsky, Franz M.
AU - Doliba, Nicolai M.
AU - Urs, Nikhil M.
AU - Caron, Marc G.
AU - Jacobson, David A.
AU - Caicedo-Vierkant, Diego A
AU - Wess, Jürgen
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85011596191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011596191&partnerID=8YFLogxK
U2 - 10.1038/ncomms14295
DO - 10.1038/ncomms14295
M3 - Article
C2 - 28145434
AN - SCOPUS:85011596191
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 14295
ER -