PROGESTERONE ADMINISTRATION INDUCED IMPAIRMENT OF INSULIN SUPPRESSIONOF HEPATIC GLUCOSE-PRODUCTION

Objective: To assess whether P administration impairs insulin-mediated glucose uptake. Design: Two-step euglycemic hyperinsulinemic clamp st udies. Setting: Rats studied with (n = 11) or without (n = 10) P treat ment. Participants: Conscious, unstressed, oophorectomized female rats . Main Outcome Measures: Plasma glucose and insulin levels and the rat es of glucose turnover results. Results: Pasting glucose (115 +/- 5 ve rsus 109 +/- 4 mg/dL conversion factor to SI units 0.05551) and insuli n (1.67 +/- 0.24 versus 1.51 +/- 0.22 ng/mL; conversion factor to SI u nits 174.5) levels were not significantly different in the control and P treated groups, respectively. However, the basal rate of glucose tu rnover was significantly higher in P-treated rats (8.38 +/- 0.50 versu s 6.59 +/- 0.35 mg/kg per minute in controls. During low-dose insulin infusion (2 mU/kg per minute), there was no difference in glucose or i nsulin levels, or the rate of glucose utilization; however, residual h epatic glucose production was significantly greater in the P group (5. 34 +/- 0.68 versus 2.57 +/- 1.00 mg/kg per minute) in controls. At hig h-dose insulin infusion (10 mU/kg per minute), hepatic glucose product ion was completely suppressed in both groups; there was no difference in insulin sensitivity as assessed by the glucose utilization rate or the ratio of glucose uptake to insulin level. Conclusions: Chronic P t herapy does not alter insulin-mediated glucose utilization in peripher al tissues but does reduce the ability of insulin to suppress endogeno us hepatic glucose production.