Plasma immunoreactive gastric inhibitory polypeptide in obese hyperglycaemic (ob/ob) mice.
Gastric inhibitory polypeptide (GIP), a recognized component of the enteroinsular axis, is raised in the plasma and intestine of obese hyperglycaemic (ob/ob) mice. To evaluate the control of plasma GIP and its role in the hyperinsulinaemia of the ob/ob syndrome, GIP and insulin were determined at different ages in fed mice, and at 10-12 weeks of age after fasting/refeeding and administration of GIP, different nutrients and insulin to mice fasted for 18 h. Plasma GIP and insulin were raised in adult (10- and 20-week-old) compared with younger (3- and 5-week-old) mice, although GIP was not increased in the presence of hyperinsulinaemia at 3 weeks of age. Fasting suppressed and refeeding promptly restored plasma GIP and insulin concentrations. Administration of GIP to mimic postprandial concentrations evoked a marked but transient insulin response which was protracted in the presence of rising hyperglycaemia. Orally administered fat, glucose and amino acids raised GIP concentrations with fat having a particularly strong effect. Glucose and amino acids also evoked prominent increases of insulin, but fat produced only a small rise in insulin in the absence of increasing glucose concentrations. Consistent with glucose-potentiation, a mixture of all three nutrients greatly augmented the insulin response without further increase of plasma GIP. Glucose-induced increase in endogenous insulin and doses of exogenous insulin up to 100 units/kg did not suppress basal, fat-stimulated or glucose-stimulated GIP release. The results indicate that raised GIP concentrations make an important contribution to the hyperinsulinaemia and related metabolic abnormalities of the ob/ob syndrome.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting; D005749:Gastric Inhibitory Polypeptide / Q000097:blood* / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000097:blood*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese / Q000097:blood*
D000596:Amino Acids; D004041:Dietary Fats; D005768:Gastrointestinal Hormones; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose