Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1-(7-36) amide (GLP-1) are glucose-dependent insulinotropic gut hormones that may explain the greater insulin secretory response with oral compared to i.v. glucose (incretin effect). To study their individual and combined contributions, in eight healthy volunteers, on separate occasions, synthetic human GIP (1 pmol/kg.min) and/or GLP-1 (0.3 pmol/kg.min) or placebo were infused i.v. (-30 to 120 min), while at 0 min, a glucose infusion "isoglycemic" to the profile after an oral glucose load of 50 g/400 mL was started. After the administration of 50 g oral glucose, immunoreactive GIP rose several-fold to 337 +/- 43 pmol/L, while there was only a transient (10-30 min) and moderate increment in immunoreactive GLP-1 (from basal, 25-30, to 41 +/- 4 pmol/L). Isoglycemic i.v. glucose infusions led to smaller B-cell responses (estimated incretin effect, 41 +/- 5%). With single infusions of GIP or GLP-1 (circulating concentrations, 464 +/- 73 and 54 +/- 3 pmol/L, respectively), B-cell responses were significantly augmented compared to i.v. glucose alone and were no longer significantly different from those after oral glucose. The combination of GIP and GLP-1 led to B-cell responses that were significantly higher than those with either hormone alone (additive mode of cooperation). Plasma GIP concentrations were similar after endogenous secretion (oral glucose) and i.v. infusion, while exogenously administered GLP-1 led to plasma levels that were maintained at an elevated level for a longer period during exogenous infusion than after stimulation by oral glucose. When, in seven volunteers, a lower dose (0.15 pmol/kg.min) of GLP-1 was infused during isoglycemic glucose infusion experiments only for the duration of elevated plasma levels in the oral glucose challenges (0-30 min), a significant, but transient, increment in insulin and C-peptide concentrations was observed, which was equivalent to 26 +/- 10% of the estimated incretin effect. Therefore, in conclusion, circulating GIP seems to make a major contribution to the incretin effect after oral glucose, and GLP-1 appears to mediate a smaller proportion. GIP and GLP-1 can interact in an additive manner in normal man.

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 [7-36 amide] (GLP-1) are glucose-dependent insulinotropic gut hormones. Under experimental conditions, both have been shown to reduce stimulated gastric acid secretion. To study their individual and combined effects on pentagastrin-stimulated (0.1 μg/kg/h from – 90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/ kg/min) or placebo (0.9% NaCl with 1 % albumin) were infused intravenously (from – 30 to 120 min) in 9 healthy volunteers. At 0 min, a glucose infusion was started that mimicked the glycemic profile after an oral glucose load of 50 g/400 ml and allowed for the glucose-dependent insulinotropic action of GIP and GLP-1 [7-36 amide]. Pentagastrin stimulated acid output significantly, but neither GIP nor GLP-1 [7-36 amide] either alone or in combination, reduced pentagastrin-stimulated gastric acid secretion. The circulating concentrations of GIP and GLP-1 [7-36 amide] obtained at steady state during exogenous administration of synthetic peptides were similar to or higher than those reached after oral glucose (endogenous secretion). In conclusion, (penta) gastrin-stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role as enterogastrone.

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Using gaseous sources of 111INC1 and 111InI with densities between 1.0.1017 cm -3 and 4.4-1019 cm -3 the perturbation of the 171.3-245.4keV 7-7 cascade was measured as a function of time and density by the time-differential perturbed angular correlation (TDPAC) method. The anisotropy shows a strong dependence on the density. By means of an extended model based on a stochastic model of Bosch and Spehl collision cross sections for charge transfer and deorientation could be determined. The cross sections for charge transfer collisions were within the region from 2-10-is cm 2 to 26.10-is cm 2 and for deorientation collisions between 1.10 -15 cm 2 and 100.10 -15 cm 2.

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