Interaction of Fat-stimulated Gastric Inhibitory Polypeptide on Pancreatic Alpha and Beta Cell Function

Abstract

A B S T R A C T Gastric inhibitory polypeptide (GIP) is considered to be the principal mediator of the enteroinsular axis. A glucose-insulin clamp technique was used to study the effects of differing blood glucose levels on the insulinotropic and glucagonotropic actions of fat-stimulated GIP in seven healthy subjects, as well as the effect of physiologic hyperinsulinemia on GIP secretion. Blood glucose levels were clamped for 4 h at 43+2 mg/dl (hypoglycemic clamp), 88+1 mg/dl (euglycemic clamp), and 141+2 mg/dl (hyperglycemic clamp) in the presence of a constant insulin infusion (100 mU/kg per h).Under hypoglycemic clamp conditions there was no increase in C-peptide nor glucagon after Lipomul ingestion, despite an increase of GIP of 51.7±8.7 ng/ml per 120 min. Under euglycemic clamp conditions, small and inconsistent increases in C-peptide and glucagon were observed after fat ingestion and a concomitant increase of GIP of 35.2±9.4 ng/ml per 120 min. Under hyperglycemic clamp conditions after fat ingestion and a GIP increase of 24.0±5.7 ng/ml per 120 min, C-peptide increased from 6.4±5 ng/ml to 11.0±1.1 ng/ml (P < 0.01) but glucagon did not change. These findings confirm that in healthy man GIP exerts its insulinotropic properties only under hyperglycemic conditions and indicate that GIP is not glucagonotropic.Under euglycemic clamp conditions (plasma glucose, 89±1 mg/dl) and physiologic hyperinsulinemia (serum immunoreactive insulin, 137±3 ,uU/ml) GIP responses to fat ingestion (39.7±9.8 ng/ml per 120 min) were not different from the GIP responses to fat ingestion in the absence of hyperinsulinemia (39.7±11.1 ng/ml per 120 min). Therefore, insulin under normogly- cemic conditions does not exert an inhibitory effect on fat-stimulated GIP secretion. The higher GIP response to oral fat in the hypoglycemic clamp, and the lower GIP response in the hyperglycemic clamp compared to the response in the euglycemic clamp suggests an effect of glycemia itself on GIP secretion in the presence of hyperinstulinemia.

Relation of immunoreactive gastric inhibitory polypeptide to changes in glycaemic control and B cell function in Type 1 (insulin-dependent) diabetes mellitus

“…The significant improvement in the glycaemic level at test 2 after 1 week with near normalization of blood glucose concentrations did not induce any change in the mean concentrations of IR-GIP before, during or after the meal and the response was not different from that of the normal subjects. The reason for the discrepancy between this study and the above mentioned (Creutzfeldt & Ebert 1977;Verdonk et al 1980) may be the heterogeneity of IR-GIP Sarson et al 1980). In the present study more than 90% of the measured immunoreactivity is the 5000-dalton GIP (Krarup et al 1983) while other antisera also detect considerable amounts of the 8000-dalton GIP and a void volume component Finkeetal.…”

“…In normal subjects the IR-GIP response to fat was diminished during a hyperglycaemic clamp when compared to that obtained during euglycaemia (Verdonk et al 1980). In untreated juvenile dia¬ betic fasting IR-GIP concentrations were markedly elevated while the IR-GIP response to a meal was insignificant (Creutzfeldt & Ebert 1977).…”

Different Effects of Glyburide and Glipizide on Insulin Secretion and Hepatic Glucose Production in Normal and NIDDM Subjects

“…Interventions that change the plasma GIP concentration could, therefore, influence the insulin response to glucose. The available information on the effects of sulfonylureas on GIP secretion is controversial (28,29), and the physiologic regulation of GIP remains unclear (30,31). In our study the basal GIP concentration in the normal subjects was either unchanged (GZ) or decreased slightly (GB) after sulfonylurea administration.…”

The Ontogeny of Serum Immunoreactive Pancreatic Lipase and Cationic Trypsinogen in the Premature Human Infant

“…For example, changes in the seum levels of gastric inhibitory polypeptide (GIP) have been shown to occur following introduction of intraduodenal amino acids and fatty acids [18]. In turn, GIP has been shown to en hance insulin secretion [19] and also pan creatic lipase production [20]. AynsleyGreen et al [21] have shown that both GIP and insulin significantly increase from basal levels, in preterm and full-term infants at birth to values in excess of mean adult fast ing values by 1-2 weeks of age.…”