Insulin releasing effects of adrenocorticotropin (ACTH 1-39) and ACTH fragments (1-24 and 18-39) in lean and genetically obese hyperglycaemic (ob/ob) mice.
An excessive insulin releasing effect of adrenocorticotropic hormone (ACTH) and ACTH fragments has been considered as a possible factor contributing to the hyperinsulinaemia of genetically obese hyperglycaemic (ob/ob) mice. To investigate this possibility, plasma glucose and insulin responses of 11- to 14-week-old fed lean and ob/ob mice were examined after intraperitoneal administration of ACTH 1-39, ACTH 1-24 and ACTH 18-39, each at a dose of 25 nmol/mouse (50-115 micrograms/mouse). ACTH 1-39 produced a marked and rapid increase of plasma insulin in both lean and ob/ob mice, the effect being much greater in the ob/ob mutant (maximum increases of 5.5 +/- 1.5 and 46.1 +/- 4.1 ng/ml at 10 min in lean and ob/ob mice respectively, P less than 0.001). In lean mice plasma glucose concentrations showed a protracted decreased (maximum decrease of 3.7 +/- 0.5 mmol/l at 120 min), whereas glucose concentrations were increased (maximum increase of 4.2 +/- 1.3 mmol/l at 60 min) in ob/ob mice. ACTH 1-24 produced qualitatively similar but generally smaller effects than ACTH 1-39, while ACTH 18-39 did not significantly affect glucose and insulin concentrations. In 24 h fasted mice, ACTH 1-39 produced similar but generally smaller effects than in fed mice. The results suggest that the effects of ACTH on glucose and insulin homoeostasis are conferred by the N-terminal 1-24 sequence, and ACTH may exert acute effects which contribute to the hyperinsulinaemia and hyperglycaemia of ob/ob mice.
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D053497:Corticotropin-Like Intermediate Lobe Peptide; D003366:Cosyntropin / Q000494:pharmacology / Q000502:physiology; D004341:Drug Evaluation; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D009765:Obesity / Q000097:blood*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D003366:Cosyntropin; D053497:Corticotropin-Like Intermediate Lobe Peptide; D000324:Adrenocorticotropic Hormone