Journal
JOURNAL OF DIABETES RESEARCH
Volume 2014, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2014/524517
Keywords
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Funding
- project of 973 [2012CB524906]
- Ministry of Science and Technology in China, NCFS [81070677]
- NSFC [81270885]
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Objective. Glucagon-like peptide-1 (GLP-1) analogues (e. g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-H-3-glucose and U-C-13-glycerol was used to measure basal rates of appearance (R-a) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-C-14-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.
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