Diurnal profiles of gastrointestinal regulatory peptides.
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Biomedical subjects
Publications and source records attributed to R Jorde.
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A systematic approach is outlined for the preparation of a whole series of immunoreactive 125I-labeled gastrointestinal regulatory peptides with high specific radioactivities. In our hands, the theoretically superior Iodo-gen method has no more to offer than the harsher chloramine-T method in the iodination of secretin, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, and motilin; whereas the gentler Iodo-gen method has to be used to obtain fully immunoreactive cholecystokinin39 (CCK39) and Tyr1-somatostatin tracers. By applying the iodination mixtures on a Sephadex G-15 or a Sephadex G-10 column followed by an SP Sephadex C-25 column--being eluted under so-called 'finite adsorption equilibrium' between the peptides to be purified and the adsorbent--highly purified tracers are obtained with unusually high specific radioactivities. Stored at -20 degrees C in diluted aliquots of from 200 to 500 microliter, these tracers can be used for radioimmunoassay purposes without rechromatography for at least 60 days.
Six healthy subjects were given a standard breakfast on one occasion and an intravenous infusion of porcine GIP in a dose of 1.0 microgram . kg-1 . h-1 on another. The experiments lasted 90 min. Plasma GIP values were determined with five different porcine GIP antisera, and, depending on the antiserum used, the postinfusion plasma GIP values could be considered both sub- and supra-physiological.
To ascertain whether an altered sensitivity to gastric inhibitory polypeptide (GIP) in morbidly obese subjects can play a role in the postprandial hyperinsulinemia seen in this condition, eight obese and eight control subjects were studied with an intravenous infusion of porcine GIP. The blood glucose was maintained at 4 mmol/l above the basal level by a hyperglycemic clamp technique. Although the mean serum insulin level was higher in the obese group throughout the study, the shapes of the serum insulin curves were almost identical in the two groups after the GIP infusion. This together with the normal GIP secretion found in obese subjects question the existence of a causal relationship between an overactive entero-insular axis and the hyperinsulinemia found in these subjects.
Eight fasting patients with non-insulin-dependent diabetes (NIDD) and six healthy controls were given an intravenous infusion of porcine gastric inhibitory polypeptide (GIP). During the GIP infusion mean plasma pancreatic polypeptide level increased significantly in both groups, whereas the mean serum insulin level increased in the NIDD group only, indicating a more important role for GIP in these patients than in healthy subjects.
Eight fasting students were given an infusion of porcine gastric inhibitory polypeptide (GIP) and glucose with or without atropine on two separate days. Mean serum insulin levels increased significantly and similarly on both occasions, indicating that both the glucose- and GIP-induced insulin release is unaffected by atropine. Plasma pancreatic polypeptide (PP) rose significantly during the GIP infusion on the day without atropine, suggesting a role for GIP in the intestinal phase of the PP release.
In an experimental study of hemorrhagic shock, systemic and portal plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin, pancreatic polypeptide (PP), gastric inhibitory peptide (GIP), secretin and insulin were measured with radioimmunoassay methods. Six pigs (30-40 kg) in general anesthesia were submitted to severe hemorrhage (approximately 30% of the blood volume) for 60 min, followed by reinfusion of the shed blood. Aortic blood pressure and cardiac output fell significantly during the shock state and recovered after the infusion. Plasma levels of somatostatin, PP, insulin and secretin rose significantly. The portal levels always presented earlier and greater elevation than did the systemic levels, except as regards secretin. No change was seen in the levels of VIP and GIP.
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Six healthy subjects were studied by means of an intravenous fat tolerance test on three occasions, in the fasting state, in the postprandial state, and during an intravenous infusion of gastric inhibitory polypeptide (GIP). No effects on the elimination rate of Intralipid were seen either by endogenous or exogenous GIP.
Plasma somatostatin was followed for 24 h in 6 healthy young males having 4 regular meals with water allowed freely, and performing their normal daily activities. Plasma somatostatin rose significantly after each meal, it returned towards the basal level before the next meal, and it rose higher and stayed significantly elevated longer after the evening meal than after any of the other meals. A possible physiological circadian rhythm of plasma somatostatin is discussed.
Six healthy subjects were given 30 min intravenous infusions of synthetic porcine GIP in doses of 0.52, 1.04 and 1.56 micrograms X kg-1 X h-1 on one occasion and a bolus injection of 1 microgram X kg-1 on another. The GIP infusions gave physiological GIP levels which did not affect plasma PP, whereas the GIP injection giving supraphysiological GIP levels evoked a significant elevation in plasma PP.
The present paper describes a sensitive, precise and specific radioimmunoassay method for measurements of plasma somatostatin; significant rises in plasma somatostatin following a test meal, intraduodenal infusion of fat and HCl, and intravenous injection of insulin; and separation of immunoreactive plasma somatostatin into two components probably representing bound and free molecular forms of somatostatin both in fasting and postprandial human plasmas.
We have earlier reported an elevation of vasoactive intestinal polypeptide (VIP) plasma levels during endotoxinaemia in pigs (Revhaug et al., 1983). In the present study the plasma levels of pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide (GIP) and insulin have been measured by sensitive Ria methods during E. coli endotoxin (Difco) shock in six anaesthetized pigs. The plasma samples were drawn from the vena porta, cava superior, internal jugular vein and the aorta. A significant increase in plasma levels of PP, somatostatin, and insulin was observed in this model. The increased plasma levels were higher in the portal vein than in the other sampling site. GIP did not present any change in this model.
Six healthy men were studied with intravenous infusions of 0.3, 1.0, and 3.0 CU/kg-h of pure porcine secretin on separate days. The secretin elimination followed a first-order kinetics. Low pharmacological doses of secretin had no significant effects on blood levels of trypsin, pancreatic amylase, insulin, somatostatin, or pancreatic polypeptide (PP), whereas high pharmacological doses significantly elevated the blood levels of trypsin, pancreatic amylase, insulin, and somatostatin but were without effect on PP.
The diurnal gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP) and insulin levels in eight morbidly obese subjects were studied before and four weeks and five months after a stapled gastric partitioning. The integrated release of all three peptides was significantly reduced postoperatively, although the profiles of the plasma GIP and PP curves were similar. On the other hand, the diurnal insulin pattern was changed from a pathological prolonged hyperinsulinemia starting shortly after breakfast and lasting till late in the evening, to a normal pattern with small, shortlived postprandial peaks.
In normal humans, significant motilin increases were found after meal ingestion, intraduodenal infusion of fat, and intraduodenal infusion of physiological HCl doses. Only a non-significant plasma motilin increase was found in response to intraduodenal infusion of cattle bile. Plasma motilin decreased significantly after an intravenous insulin injection. During routine cardiac catheterization in a group of 10 patients plasma motilin was significantly lower in the renal vein than in the femoral vein, femoral artery, right atrium, and hepatic vein, suggesting that the kidneys participate in the removal of motilin from the circulation. Fasting and oral fat-stimulated plasma motilin immunoreactivity eluted in two peaks on a Sephadex G-50 Fine column. The two peaks behaved identically with porcine motilin in dilution series.
Nine morbidly obese subjects were studied with a test meal before and 3 months after a gastric partitioning operation. After the operation the postprandial release of plasma gastric inhibitory polypeptide was significantly increased, the plasma pancreatic polypeptide release was similar, and the serum insulin release significantly reduced as compared with the preoperative values.
Twenty-three morbidly obese and 17 control subjects were studied with a breakfast meal. Neither fasting nor postprandial plasma pancreatic polypeptide (PP) levels differed significantly between the two groups, whereas postprandial serum insulin and blood glucose were significantly higher in the obese subjects. Our results do not support the suggestion that PP participates in the appetite regulation or the development of obesity.