Dose-response relationship of insulin to glucose fluxes in the awake and unrestrained mouse

The purpose of the study was to use the hyperinsulinemic-euglycemic clamp t echnique to generate insulin dose-response curves for insulin suppression o f endogenous glucose output (EGO) and stimulation of the glucose disposal r ate (GDR) in conscious unstressed mice. Five groups of male ICR (Institute for Cancer Research) mice were studied (N = 43), The animals underwent surg ery for implantation of a jugular vein catheter 2 to 3 days before the clam p and were fasted 6 hours before the study. Each group was clamped at a dif ferent insulin infusion rate of 0, 2.5, 10, or 20 mU/kg/min. H-3-3-glucose was infused for measurement of the glucose turnover rate (rate of appearanc e [Ra]), Blood samples were collected by milking a severed tail-tip. EGO wa s calculated as the difference between the Ra and glucose infusion rate (GI R), and the glucose clearance rate (GCR) as the GDR divided by the plasma g lucose concentration. From the curves generated, half-maximal EGO and GCR w ere obtained at a plasma insulin concentration of 20 to 30 mu U/mL, which w as achieved at an insulin infusion rate of about 4 to 5 mU/kg/min, Maximal suppression of EGO and stimulation of the GCR occurred at an insulin infusi on rate of 10 mU/kg/min, The establishment of normative curves for insulin- stimulated glucose metabolism in conscious mice facilitates the evaluation of glucose metabolism in a variety of mouse models of insulin resistance. C opyright (C) 1999 by W.B. Saunders Company.