Rapid induction of insulin resistance in opioid mu-receptor knock-out mice.
Role of opioid mu-receptor that has been showed to involve in the insulin-dependent diabetic rats in the induction of insulin resistance remains unclear. The present study is performed to clarify this point. The wild-type mice or opioid mu-receptor knockout mice were employed to induce insulin resistance by feeding with fructose-rich chow or by the repeated intraperitoneal injections of long-acting form of human insulin at 0.5 IU/kg three times daily. The basal plasma glucose concentration was not markedly changed in fructose-fed mice regardless the presence of opioid mu-receptor or not. However, the plasma glucose lowering activity of tolbutamide (10.0 mg/kg) disappeared rapidly in opioid mu-receptor knockout mice receiving fructose-rich chow as compared to that in wild type group. In opioid mu-receptor knockout mice, the elevation of plasma glucose concentration and the loss of plasma glucose lowering activity of tolbutamide were observed at 15 days after insulin injection. However, similar change was obtained at 21 days later of insulin injection in wild-type mice, showing that decrease of insulin action was more markedly in opioid mu-receptor knockout mice. Our results indicated that opioid mu-receptor is related to the delay of insulin resistance induced by fructose-fed method or insulin repeated injection.
Cheng
Juei-Tang
JT
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 70101. jtcheng@mail.ncku.edu.tw
Liu
I-Min
IM
Hsu
Chih Fen
CF
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D005508:Food Deprivation; D005632:Fructose / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017450:Receptors, Opioid, mu; D005632:Fructose; D014044:Tolbutamide