期刊
DIABETES
卷 59, 期 10, 页码 2653-2661出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-1564
关键词
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资金
- National Institutes of Health [R01-HL075675, R01-HL09333, AT0-02599, AT0-02993, AT0-03545]
- National Institutes of Health through University of Washington Diabetes Endocrinology Research Center [P30 DK-17047]
OBJECTIVE-The efficacy of liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, to prevent or delay diabetes in UCD-T2DM rats, a model of polygenic obese type 2 diabetes, was investigated. RESEARCH DESIGN AND METHODS-At 2 months of age, male rats were divided into three groups: control, food-restricted, and liraglutide. Animals received liraglutide (0.2 mg/kg s.c.) or vehicle injections twice daily. Restricted rats were food restricted to equalize body weights to liraglutide-treated rats. Half of the animals were followed until diabetes onset, whereas the other half of the animals were killed at 6.5 months of age for tissue collection. RESULTS-Before diabetes onset energy intake, body weight, adiposity, and liver triglyceride content were higher in control animals compared with restricted and liraglutide-treated rats. Energy-restricted animals had lower food intake than liraglutide-treated animals to maintain the same body weights, suggesting that liraglutide increases energy expenditure. Liraglutide treatment delayed diabetes onset by 4.1 +/- 0.8 months compared with control (P < 0.0001) and by 1.3 +/- 0.8 months compared with restricted animals (P < 0.05). Up to 6 months of age, energy restriction and liraglutide treatment lowered fasting plasma glucose and A1C concentrations compared with control animals. In contrast, liraglutide-treated animals exhibited lower fasting plasma insulin, glucagon, and triglycerides compared with both control and restricted animals. Furthermore, energy-restricted and liraglutide-treated animals exhibited more normal islet morphology. CONCLUSIONS-Liraglutide treatment delays the development of diabetes in UCD-T2DM rats by reducing energy intake and body weight, and by improving insulin sensitivity, improving lipid profiles, and maintaining islet morphology. Diabetes 59:26532661, 2010
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