Progesterone administration induced impairment of insulin suppression of hepatic glucose production

Objective: To assess whether P administration impairs insulin-mediated glucose uptake. Design: Two-step euglycemic hyperinsulinemic clamp studies. Setting: Rats studied with (n = 11) or without (n = 10) P treatment. Participants: Conscious, unstressed, oophorectomized female rats. Main Outcome Measures: Plasma glucose and insulin levels and the rates of glucose turnover results. Results: Fasting glucose (115 ± 5 versus 109 ± 4 mg/dL; conversion factor to SI units 0.05551) and insulin (1.67 ± 0.24 versus 1.51 ± 0.22 ng/mL; conversion factor to SI units 174.5) levels were not significantly different in the control and P treated groups, respectively. However, the basal rate of glucose turnover was significantly higher in P- treated rats (8.38 ± 0.50 versus 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 insulin levels, or the rate of glucose utilization; however, residual hepatic 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 high-dose insulin infusion (10 mU/kg per minute), hepatic glucose production 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 therapy does not alter insulin-mediated glucose utilization in peripheral tissues but does reduce the ability of insulin to suppress endogenous hepatic glucose production.