期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 302, 期 8, 页码 E924-E931出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00198.2011
关键词
obesity; diabetes; adenosine 5 '-monophosphate-activated protein kinase
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health, Labor, and Welfare of Japan
- Japan Foundation for Applied Enzymology
- Fujiwara Memorial Foundation
- Grants-in-Aid for Scientific Research [22126012, 21229013, 21591175, 23126514, 23791054, 24390237, 23659476, 22591010] Funding Source: KAKEN
Amylin improves the effect of leptin on insulin sensitivity in leptin-resistant diet-induced obese mice. Am J Physiol Endocrinol Metab 302: E924-E931, 2012. First published January 24, 2012; doi:10.1152/ajpendo.00198.2011.-Leptin enhances insulin sensitivity in addition to reducing food intake and body weight. Recently, amylin, a pancreatic beta-cell-derived hormone, was shown to restore a weight-reducing effect of leptin in leptin-resistant diet-induced obesity. However, whether amylin improves the effect of leptin on insulin sensitivity in diet-induced obesity is unclear. Diet-induced obese (DIO) mice were infused with either saline (S), leptin (L; 500 mu g.kg(-1).day(-1)), amylin (A; 100 mu g.kg(-1).day(-1)), or leptin plus amylin (L/A) for 14 days using osmotic minipumps. Food intake, body weight, metabolic parameters, tissue triglyceride content, and AMP-activated protein kinase (AMPK) activity were examined. Pair-feeding and weight-matched calorie restriction experiments were performed to assess the influence of food intake and body weight reduction. Continuous L/A coadministration significantly reduced food intake, increased energy expenditure, and reduced body weight, whereas administration of L or A alone had no effects. L/A coadministration did not affect blood glucose levels during ad libitum feeding but decreased plasma insulin levels significantly (by 48%), suggesting the enhancement of insulin sensitivity. Insulin tolerance test actually showed the increased effect of insulin in L/A-treated mice. In addition, L/A coadministration significantly decreased tissue triglyceride content and increased AMPK alpha 2 activity in skeletal muscle (by 67%). L/A coadministration enhanced insulin sensitivity more than pair-feeding and weight-matched calorie restriction. In conclusion, this study demonstrates the beneficial effect of L/A coadministration on glucose and lipid metabolism in DIO mice, indicating the possible clinical usefulness of L/A coadministration as a new antidiabetic treatment in obesity-associated diabetes.
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