title: Progesterone administration induced impairment of insulin suppression of hepatic glucose production.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: T
authors.initials: T
authors.lastname: Nelson
authors.forename: G
authors.initials: G
authors.lastname: Shulman
authors.forename: D
authors.initials: D
authors.lastname: Grainger
authors.forename: M P
authors.initials: MP
authors.lastname: Diamond
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011374:Progesterone; D005947:Glucose