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 3-3H-glucose and U-13C-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-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal R a of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, R a 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.
CITATION STYLE
Wu, H., Sui, C., Xu, H., Xia, F., Zhai, H., Zhang, H., … Lu, Y. (2014). 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. Journal of Diabetes Research, 2014. https://doi.org/10.1155/2014/524517
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