Interaction of fat-stimulated gastric inhibitory polypeptide on pancreatic alpha and beta cell function

C. A. Verdonk, R. A. Rizza, R. L. Nelson, V. L. Go, J. E. Gerich, F. J. Service

Research output: Contribution to journalArticle

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Abstract

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 conditons 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 condtions, 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 μU/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 normoglycemic 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 hyperinsulinemia.

Original languageEnglish (US)
Pages (from-to)1119-1125
Number of pages7
JournalJournal of Clinical Investigation
Volume65
Issue number5
StatePublished - 1980

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Glucagon-Secreting Cells
Gastric Inhibitory Polypeptide
Insulin-Secreting Cells
Fats
Glucose Clamp Technique
Hyperinsulinism
Eating
C-Peptide
Glucagon
Hypoglycemic Agents
Insulin
Blood Glucose
Corn Oil

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Verdonk, C. A., Rizza, R. A., Nelson, R. L., Go, V. L., Gerich, J. E., & Service, F. J. (1980). Interaction of fat-stimulated gastric inhibitory polypeptide on pancreatic alpha and beta cell function. Journal of Clinical Investigation, 65(5), 1119-1125.

Interaction of fat-stimulated gastric inhibitory polypeptide on pancreatic alpha and beta cell function. / Verdonk, C. A.; Rizza, R. A.; Nelson, R. L.; Go, V. L.; Gerich, J. E.; Service, F. J.

In: Journal of Clinical Investigation, Vol. 65, No. 5, 1980, p. 1119-1125.

Research output: Contribution to journalArticle

Verdonk, CA, Rizza, RA, Nelson, RL, Go, VL, Gerich, JE & Service, FJ 1980, 'Interaction of fat-stimulated gastric inhibitory polypeptide on pancreatic alpha and beta cell function', Journal of Clinical Investigation, vol. 65, no. 5, pp. 1119-1125.
Verdonk, C. A. ; Rizza, R. A. ; Nelson, R. L. ; Go, V. L. ; Gerich, J. E. ; Service, F. J. / Interaction of fat-stimulated gastric inhibitory polypeptide on pancreatic alpha and beta cell function. In: Journal of Clinical Investigation. 1980 ; Vol. 65, No. 5. pp. 1119-1125.
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abstract = "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 conditons 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 condtions, 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 μU/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 normoglycemic 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 hyperinsulinemia.",
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