Effect of graded intraduodenal glucose infusions on the release and physiological action of gastric inhibitory polypeptide

A. J. McCullough, Laurence J Miller, F. J. Service, V. L W Go

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30 Scopus citations


Gastric inhibitory polypeptide (GIP) is the leading candidate for gut hormonal augmentation of insulin release. The release of its subspecies (mol wt, 5,000 and 7,500) and the physiological action of total immunoreactive GIP (IR-GIP) were investigated during isotonic glucose infusions at 75, 225, and 465 mg/min in nine volunteers. Each dose was infused intraduodenally and iv in the same volunteer. Intestinal augmentation of insulin release occurred during the high dose intraduodenal glucose infusion (P < 0.001) but not during the lower doses. An elevation of 17-20 mg/dl in plasma glucose was required before this insulinotropic effect occurred (P < 0.001). At increments of plasma glucose above 17 mg/dl, the augmentation of gut-mediated insulin release was dependent on the degree of hyperglycemia (r = 0.81; P < 0.01). At each dose of intraduodenally administered glucose, IR-GIP was elevated within 20-40 min (P < 0.01), remaining at a steady level until the infusion was stopped. The release of IR-GIP was proportional to the intestinal glucose load but was unchanged from the basel level during iv glucose studies. The attained IR-GIP levels remained constant in each study despite large variations over time in plasma glucose and insulin concentrations. During intestinal glucose infusion, 58.7 ± 4.1% of IR-GIP was accounted for by the 5,000 mol wt subspecies and 17.3 ± 3.5% was accounted for by the 7,500 mol wt subspecies, with the remaining immunoreactivity found in the void volume of a Sephadex G-50 column. Relative proportions remained constant throughout the 4-h study. Thus during glucose stimulation, the total IR-GIP released (1) is proportional to the absorbable luminal stimulus, (2) is independent of ambient plasma insulin and glucose levels, (3) is composed predominantly of the 5,000 mol wt form, and (4) requires an elevation in plasma glucose of 17-20 mg/dl before it augments insulin release, but then stimulates insulin release in a fashion linearly dependent upon the increment in plasma glucose.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - 1983


ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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