期刊
ENDOCRINOLOGY
卷 150, 期 11, 页码 4874-4882出版社
ENDOCRINE SOC
DOI: 10.1210/en.2009-0454
关键词
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资金
- University of Texas Southwestern Medical Center at Dallas [PL1 DK081182-01]
- National Institutes of Health [1F32DK066972, K99HD056491, K99DK085330, PO1 DK56116, DK53301, GM41890, R01 DK53301-07S2, R01 CA134502-01]
- V Foundation
- Canadian Institute of Health Research
- American Diabetes Association Smith Family Foundation
- Takeda Pharmaceutical Co., Ltd., Japan
Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85 alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110 alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis. (Endocrinology 150: 4874-4882, 2009)
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