Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity.

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.

Circadian rhythm of gastric inhibitory polypeptide (GIP) in man.

The diurnal variations of serum gastric inhibitory polypeptide (GIP), serum insulin, plasma glucagon, plasma glucose and serum triglycerides were studied for 24 hr in 6 healthy young men, consuming three meals and performing their usual physical activities. Serum GIP levels peaked after each meal and stayed significantly elevated from the peak after lunch till late night. Glucose and insulin showed early and short-lasting postprandial peaks, declining thereafter to basal values within a short time. Plasma glucagon was inhibited by the meal ingestion and fluctuated around the basal levels in the interdigestive periods. On the other hand, serum triglycerides tended to parallel GIP changes for most of the day, being significantly elevated starting from lunch consumption to late night. The present results suggest that GIP may have effects other than the insulinogenic one, being probably involved in the control of lipid metabolism.

Peptides of the APUD system in amphibian skins.

Methanol extracted skins from 84 species of amphibia were screened, measuring by RIAs: gastrin-CCK, VIP, calcitonin, GIP, PP and motilin. G-CCK-like immunoreactivity was found in 97.6%; VIP-like immunoreactivity in 41%; CT-like immunoreactivity in 34%; GIP-like immunoreactivity in 10%; PP-like immunoreactivity in 40% and MT-like immunoreactivity in 60% of the samples. The use of a sequence-specific radioimmunoassay and of gel-chromatography confirmed the caerulein-CCK-8-like nature of the immunoreactive material. Detected amounts of the other peptides (VIP, CT, GIP, PP, MT) were too low for bioassay or chromatographic studies, thus leaving the question open if they are due to some kind of unspecific interferences or, most likely, to species-specificity differences of the used antisera.

Optimal nutritional indexes in gastroenterology.

Malnutrition in gastrointestinal disease can result from several pathogenetic mechanisms. The resulting clinical and laboratory features of malnutrition vary according to the specific pathogenetic factors involved. Many of the causes of malnutrition in gastroenterology are similar to those found in other acute and chronic diseases. However, certain disorders, specific to gastroenterology, may alter nutritional indices independent of the usual causes of malnutrition. These include small bowel bacterial overgrowth and protein-losing enteropathy. The impact of these disorders on the indexes of nutritional status is discussed.

Effect of various stimulants and inhibitors of gastric acid secretion on mucosal potential difference in man.

Pentagastrin and histamine in doses effective in stimulating gastric acid secretion (5 microgram/kg/h intravenously and 25 microgram/kg intramuscularly, respectively) produce a significant decrease in the gastric mucosal potential difference (PD) in man. In contrast, atropine and cimetidine (2 mg/30 min intravenously and 4.5 mg/kg/h intravenously respectively) cause a significant increase in gastric PD. The subsequent or simultaneous administration of cimetidine reverses the effect of the stimulating agents on gastric PD and pH. Similarly, the subsequent administration of pentagastrin reverses the effect of atropine. The intragastric instillation of 100 c HCl 0.1 N increases significantly the gastric PD valuesp in this case the patterns of PD and pH changes are dissimilar. This study indicates that substances that modify gastric acid secretion also induce changes in gastric PD; this last effect does not seem to depend on variations of the intragastric pH. Therefore, in the clinical evaluation of the gastric PD in man, its multifactorial origin must alway be considered.

Effect of somatostatin on fasting and glucose-stimulated gastric inhibitory polypeptide release in man.

The effect of intravenous somatostatin infusion on circulating gastric inhibitory polypeptide (GIP), insulin, glucagon and on blood glucose was investigated in 7 healthy volunteers in the fasting state and during the oral ingestion of 75 g glucose. Somatostatin (1.1 microgram/kg/h) infused 30 min before and continued 60 min after the ingestion of glucose did not affect fasting levels of any of the above parameters while it significantly suppressed the GIP and insulin response to glucose. The same somatostatin dose infused 30 min after the ingestion of glucose decreased significantly the raised levels of GIP and insulin and further increased blood glucose levels. It is concluded that somatostatin inhibits GIP release mainly at the level of the GIP-producing cells.

Adrenergic modulation of gastric inhibitory polypeptide secretion in man.

In order to examine the effect of adrenergic influences on gastric inhibitory polypeptide (GIP) secretion, a series of glucose tolerance tests was carried out in seven healthy volunteers during intravenous infusion of epinephrine (6 microgram/min), epinephrine plus phentolamine (5 mg stat + 0.5 mg/min), epinephrine plus propranolol (5 mg stat + 0.08 mg/min), and saline. No drug infusion modified fasting GIP levels. Alpha-adrenergic stimulation (epinephrine + propranolol) significantly reduced the GIP response (P less than 0.02) and completely inhibited the insulin response (P less than 0.005) to oral glucose, compared with control experiments. Epinephrine alone and epinephrine + phentolamine did not influence glucose-stimulated GIP. These results suggest the possibility that the adrenergic nervous system may have a role in the regulation of GIP secretion in man.