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Ten normal volunteers ingested emulsified corn oil and the immunoreactive GIP, insulin (IRI) and nonesterified fatty acid (NEFA) responses were measured. Serum GIP levels increased after the ingestion of corn oil in all subjects, rising from a mean fasting level of 272 pg/ml to 856 +/- 272 pg/ml (P less than 0.05) by 30 minutes. The peak mean serum GIP concentration of 1,345 +/- 291 pg/ml occurred at 60 minutes; and mean serum GIP levels at 180 minutes remained significantly elevated over fasting values. Serum IRI, glucose and NEFA concentrations did not change during the 180 minutes of study. No changes in serum GIP concentrations occurred when, for control purposes, six volunteers ingested water on another day. We conclude: 1) Fat is a potent stimulus for the release of GIP in normal individuals. 2) Endogenously released GIP is not insulinotropic under the conditions of this study.

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Serum pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), insulin and glucose responses to meal stimulation were studied in 10 normal weight patients, 13 normal obese patients and 7 patients with Prader-Willi syndrome (PWS) associated obesity. Serum and plasma concentrations of PP, glucose, insulin and GIP were obtained at 15 min intervals from 0-180 min. after a 275 K calorie meal. Basal and peak responses of glucose, for patients with PWS were significantly lower when compared to normal or obese controls. Basal and peak insulin responses in PWS were significantly greater than those of the normal controls but still less than those of the obese controls. Basal GIP concentrations in the patients with PWS were significantly less than normals and their peak response was less than the obese control group. No significant differences in basal or peak PP responses were noted between normal and obese controls. All 7 patients with PWS had abnormal PP responses. Five failed to show significant PP release after the stimulation; one had a peak response to 130 pg/ml while the 7th patient (PB) had an exaggerated response to 2000 pg/ml. The 6 patients with low or no response had basal PP values of 62 +/- 12 pg/ml and a mean PP peak response of 78 +/- 15 pg/ml. This observation of blunted PP response in a human model of hyperphagia and obesity parallels the animal models and suggests PP may have a significant role in appetite control.

Serum GIP, insulin, and glucose concentrations were determined during a standard oral glucose tolerance test in 80 individuals, 45 of whom were normal and 35 of whom had adult-onset diabetes mellitus according to USPHS criteria. As a group, the diabetics had fasting hyperglycemia (219 +/- 17 mg./dl.) and, in response to glucose, displayed a peak serum glucose of 373 +/- 23 mg./dl. and sustained hyperglycemia (315 +/- 24 mg./dl.) at 180 minutes. There were no statistically significant differences in absolute serum insulin levels between the two groups. However, insulin secretion was delayed, IRI increments were smaller, and the IRI concentrations were inappropriately low for the simultaneous serum glucose concentrations in the diabetics at every time interval tested. Mean fasting serum GIP was 335 +/- 30 pg./ml. in the diabetics as against 262 +/- 15 pg./ml. in normal individuals (p less than 0.025). After the ingestion of glucose, diabetics had significantly higher (p less than 0.001) mean serum GIP levels between five and 120 minutes. By 180 minutes, serum GIP levels remained above fasting in both groups, but the diabetics had higher than normal serum concentrations (p less than 0.05). Peak serum GIP concentrations, which occurred at 30 minutes in both groups, were 1,376 +/- 106 and 806 +/- 75 pg./ml. in the diabetics and normals, respectively (p less than 0.001). Total integrated serum GIP was also greater in diabetics than normals (140,852 +/- 14,208 vs. 64,602 +/- 8,719 pg.-min./ml.-1, p less than 0.001). The higher serum GIP concentrations observed following glucose ingestion in diabetics could not be attributed to obesity or age. We conclude that both fasting and glucose-stimulated GIP concentrations are higher than normal in obese adult-onset diabetics. The significance of this observation is uncertain. However, since our current understanding suggests the GIP may be an important enteric signal for the release of insulin in man, and because GIP has been shown to stimulate the release of immunoreactive glucagon, GIP may play a role in the pathogenesis of diabetes mellitus.

Children with hyperphagia and obesity of Prader-Willi syndrome (PWS) have previously been shown to have blunted pancreatic polypeptide (PP) response to low protein meal stimulation. To evaluate the effects of various protein challenges on PP release in children with PWS, we administered both a low protein (0.2 g/kg) and a high protein (2.0 g/kg) meal stimulation test to 12 children previously diagnosed as having PWS and to an age- and weight-matched group of 19 obese but otherwise normal children. Serum samples were collected just before and for 3 h after meal ingestion. The mean (+/- SD) age was 11.7 +/- 4.2 yr for the PWS group and 10.3 +/- 3.8 yr for the obese group (P = 0.323). The percent ideal body weight for height for the PWS group (mean +/- SD 186 +/- 48%) was not significantly different from the percent ideal body weight for height for the obese group (174 +/- 35%; P = 0.421). Peak PP responses were significantly less for the PWS group than for the obese group for both the low and high protein meal stimulations. The mean (+/- SE) peak PP response with the low protein meal was 76.1 +/- 13 pg/ml for the PWS group and 302 +/- 93 pg/ml for the obese group (P less than 0.05). The mean peak response with the high protein meal was 181 +/- 51 pg/ml for the PWS group and 581 +/- 127 pg/ml for the obese group (P less than 0.01). Glucose rises were similar for both tests, although the PWS group did have a slightly smaller rise in glucose after the low protein stimulation than was observed in the obese group. The insulin response was also significantly less for the low protein meal in the PWS group compared to the low protein insulin response of the obese group. There were no significant differences in the insulin responses observed in both groups with the high protein meal test. This study confirms our previous observation and suggests that many children with PWS have a functional deficiency of PP. Our current study demonstrates that this condition is not a result of their obese condition or an alteration in their response threshold to protein.

Intravenously administered porcine GIP is insulinotropic in man. This study was designed to investigate the effects of simultaneous fat ingestion, a potent stimulus for GIP release, and intravenous glucose infusion upon endogenous serum GIP and insulin concentrations in normal subjects. Seven normal volunteers were studied on three separate occasions following: a) the ingestion of 67 grams of emulsified corn oil, b) constant intravenous infusion of glucose, and c) simultaneous administration of corn oil and glucose as in parts (a) and (b) of the study. Serum glucose, insulin (IRI), and GIP concentrations were measured at intervals between 15 and 180 minutes following each stimulus. With corn oil, mean serum GIP concentrations increased from a fasting level of 290 +/- 40 (SE) pg/ml to 1936 +/- 402 pg/ml at 60 minutes without a significant change in serum IRI or glucose concentrations. The infusion of intravenous glucose alone was associated with no rise in serum GIP levels despite a substantial increase in serum IRI and glucose concentrations. With the combined stimuli, mean serum GIP increased less (P is less than .05) between 30 and 90 minutes, and total integrated incremental GIP was significantly less (P is less than .025) than that after corn oil ingestion alone. Following the combined stimuli, incremental insulin levels were higher (P is less than .05) between 15 and 90 minutes, total integrated incremental insulin was greater (P is less than .025), and glucose homeostasis was significantly enhanced (P is less than .05) at 120 and 180 minutes compared with the effects on insulin of glucose infusion alone. We conclude that the potentiation of glucose-stimulated insulin secretion induced by the ingestion of fat is associated with serum GIP levels that are within the insulinotropic range. The augmented secretion of insulin may be mediated partially or completely by endogenous GIP. The lower serum GIP concentrations observed following the combined stimuli suggest a feedback inhibition of GIP release which is perhaps mediated by insulin.

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