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The GLP-1 analogue exenatide improves hepatic and muscle insulin sensitivity in diabetic rats: tracer studies in the basal state and during hyperinsulinemic-euglycemic clamp.

Abstract：

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-(3)H-glucose and U-(13)C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-(14)C-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.

journal_name

J Diabetes Res

journal_title

Journal of diabetes research

authors

Wu H,Sui C,Xu H,Xia F,Zhai H,Zhang H,Weng P,Han B,Du S,Lu Y

doi

10.1155/2014/524517

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

524517

eissn

2314-6745

issn

2314-6753

journal_volume

2014

pub_type

杂志文章

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