Progesterone administration induced impairment of insulin suppression of hepatic glucose production.
OBJECTIVE
To assess whether P administration impairs insulin-mediated glucose uptake.


METHODS
Two-step euglycemic hyperinsulinemic clamp studies.


METHODS
Rats studied with (n = 11) or without (n = 10) P treatment.


METHODS
Conscious, unstressed, oophorectomized female rats.


METHODS
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.
Nelson
T
T
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.
Shulman
G
G
Grainger
D
D
Diamond
M P
MP
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D011374:Progesterone; D005947:Glucose