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

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. © 2014 hui wu et al.