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PTEN deletion in pancreatic α-cells protects against high-fat diet-induced hyperglucagonemia and insulin resistance.
- Source :
-
Diabetes [Diabetes] 2015 Jan; Vol. 64 (1), pp. 147-57. Date of Electronic Publication: 2014 Aug 04. - Publication Year :
- 2015
-
Abstract
- An aberrant increase in circulating catabolic hormone glucagon contributes to type 2 diabetes pathogenesis. However, mechanisms regulating glucagon secretion and α-cell mass are not well understood. In this study, we aimed to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling is an important regulator of α-cell function. Mice with deletion of PTEN, a negative regulator of this pathway, in α-cells show reduced circulating glucagon levels and attenuated l-arginine-stimulated glucagon secretion both in vivo and in vitro. This hypoglucagonemic state is maintained after high-fat-diet feeding, leading to reduced expression of hepatic glycogenolytic and gluconeogenic genes. These beneficial effects protected high-fat diet-fed mice against hyperglycemia and insulin resistance. The data demonstrate an inhibitory role of PI3K signaling on α-cell function and provide experimental evidence for enhancing α-cell PI3K signaling for diabetes treatment.<br /> (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
- Subjects :
- Animals
Arginine metabolism
Diabetes Mellitus, Type 2 genetics
Diet, High-Fat
Female
Glucagon metabolism
Glucagon-Secreting Cells cytology
Glucagon-Secreting Cells metabolism
Hyperglycemia genetics
Hyperglycemia metabolism
Insulin-Secreting Cells cytology
Insulin-Secreting Cells physiology
Male
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Transgenic
PTEN Phosphohydrolase metabolism
Phosphatidylinositol 3-Kinases metabolism
RNA, Small Interfering genetics
Signal Transduction physiology
Diabetes Mellitus, Type 2 metabolism
Glucagon blood
Glucagon-Secreting Cells physiology
Insulin Resistance physiology
PTEN Phosphohydrolase genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 64
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 25092678
- Full Text :
- https://doi.org/10.2337/db13-1715