Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats.
Our previous work has suggested the presence of an insulin resistance in the adult offspring of streptozotocin-diabetic pregnant rats. In this study we used the euglycaemic hyperinsulinaemic clamp technique with an isotope-dilution method to define and quantify this postulated insulin resistance in adult offspring of streptozotocin-diabetic rats. Under basal conditions, these rats had a lower body weight than control rats, but their glucose and insulin concentrations were normal. During the hyperinsulinaemic clamp, the steady-state glucose infusion rate was significantly lower in the offspring of streptozotocin-diabetic rats than in both age- and weight-matched controls, indicating insulin resistance. Basal peripheral tissue glucose utilization was normal in the offspring of streptozotocin-diabetic rats, but the dose-response curve was shifted to the right:insulin concentrations causing half-maximal stimulation of glucose utilization were increased by about 60% in the offspring of diabetic rats; the maximal stimulation of glucose utilization, however, was unaltered. Basal hepatic glucose production was normal, but again, half-maximal suppression of glucose production occurred at insulin concentrations 50% higher than in control rats; in addition, the maximal suppression of glucose production was significantly decreased, even at insulin concentrations of 5700 microU/ml. These data are evidence for an insulin resistance in the adult offspring of streptozotocin-diabetic rats, characterized by: (1) a decreased insulin sensitivity by peripheral glucose-utilizing tissues, and, (2) a decreased sensitivity and responsiveness of the liver.
Holemans
K
K
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, Belgium.
Aerts
L
L
Van Assche
F A
FA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007332:Insulin Infusion Systems; D007333:Insulin Resistance; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon