Combined effect of growth hormone and cortisol on late posthypoglycemic insulin resistance in humans.
The occurrence and mechanisms for late (6.5- to 7.5-h) posthypoglycemic insulin resistance were studied with the euglycemic clamp in 19 healthy subjects. Comparisons were made with a control study with the same insulin infusion rate but where hypoglycemia was prevented by glucose infusion. Glucose production and utilization were studied with D-[3-3H] glucose infusions. Hypoglycemia induced marked insulin resistance shown by lower glucose infusion rates compared with the control study 3.1 +/- 0.3 vs. 6.0 +/- 0.7 mg.kg-1.min-1, P less than .001). This late posthypoglycemic insulin resistance was mainly due to a decreased insulin effect on glucose utilization. Infusion of propranolol did not prevent insulin resistance, whereas somatostatin partially prevented its appearance. Somatostatin plus metyrapone completely normalized posthypoglycemic insulin resistance. A positive correlation (r = .72, P less than .001) was found between initial insulin sensitivity and percent reduction of the insulin effect after hypoglycemia. Thus, hypoglycemia is followed by prolonged (6- to 8-h) insulin resistance. In contrast to early-phase (2- to 3-h) resistance, long-term resistance is not due to beta-adrenergic stimulation but to the combined effect of growth hormone and cortisol. This resistance is also more pronounced in subjects with initially high insulin sensitivity.
Fowelin
J
J
Department of Medicine II, Sahlgren's Hospital, University of Göteborg, Sweden.
Attvall
S
S
Von Schenck
H
H
Smith
U
U
Lager
I
I
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007003:Hypoglycemia / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013004:Somatostatin; D011433:Propranolol; D005947:Glucose; D006854:Hydrocortisone; D004837:Epinephrine; D008797:Metyrapone