Kerstin Uvnäs‐Wallensten

Effects of Somatostatin on Gastrointestinal Propagation and Absorption of Oral Glucose in Man

The effects of i.v. somatostatin, 6.0–0.05 μg · min-1, on the gastric emptying and on the transit times and glucose absorption in the proximal 70 cm of the small bowel after 75 g of oral glucose were examined in healthy subjects with a multiple-marker dilution method. In the controls the stomach emptied the hypertonic glucose solution in 3 h and 48 ± 4 g of glucose was absorbed in the intestinal test segment. Approximately even proportions were absorbed from the emptied glucose portions throughout the experiments; variations were caused by the varying transit time, the absorption being more complete the longer the time to transit the segment. Somatostatin, started 20 min before oral glucose and infused for 1 or 2 h, prolonged dose-dependently the transit time. A maximal prolongation from 15 ± 2 min in the controls to 55 ± 7 min (p -1, and 0.05 μg · min-1 somatostatin gave a significant twofold slowing. The inhibition of the intestinal motility persisted in the postinfusion period and was followed by a late sudden acceleration of the propagation speed. The gastric emptying rate was reduced by somatostatin, but the inhibition was slowly established and of marginal consequences for the absorption. 2-Hour infusions of more than 1.5 μg · min-1 delayed the complete emptying. Somatostatin reduced dose-dependently the glucose absorption rate in the segment. In the controls the absorption rate of 9.5 ± 1.4% · min-1 of transit decreased to 4.2 ± 0.7% min-1 (p -1 and to 2.6 ± 0.1 % · min-1 (p -1 of somatostatin and was further lowered by higher doses. The lower effectiveness was compensated by the prolonged transit times so that the totally absorbed glucose in the segment approached the control value. An absolute reduction was only recorded in early phases of the experiments before the transit was slowed and it seems to result in spite of prolonged transit from infusion rates of 1.5 μg · min-1 or more somatostatin. Dose-related side effects from the digestive tract and due to hypoglycemia in the late postinfusion period were common with infusion rates exceeding 0.5 μg · min-1. The study shows that exogenous somatostatin delays and evens out the uptake of oral glucose in the proximal small bowel by dose-dependent inhibitory effects on the gastrointestinal motility and reductions of the glucose absorption rate. The effects could be produced by somatostatin doses a hundred times lower than previously tested for effects in the human gastrointestinal tract.

Effects of short-time somatostatin infusion on the gastric and intestinal propulsion in humans.

The effect of short-time somatostatin infusion on gastric and intestinal propulsion of an oral glucose load was examined in healthy subjects by means of a multiple indicator dilution technique. The early gastric emptying rate was enhanced by somatostatin, indicating delayed gastric inhibition. After withdrawal of the somatostatin infusion, the late gastric emptying rate was decreased and the intestinal propagation rate markedly slowed. The effect of long-time somatostatin infusion has to be examined to analyse the nature of the events described.

Effects of Graded Doses of Somatostatin on Gallbladder Emptying and Pancreatic Enzyme Output after Oral Glucose in Man

Effects of intravenous somatostatin on the secretion, motility and absorption in the upper gastrointestinal tract after 75 g oral glucose were examined in healthy subjects with a quantitative multiple indicator dilution method. This report deals with the effects on the gallbladder emptying and the pancreatic enzyme output. Intake of a hypertonic glucose solution induces rapid gallbladder emptying. After early peaks, both biliary and pancreatic enzyme outputs remain at a steady lower level to the end. Somatostatin, started 20 min before the oral load, inhibited dose-dependently the gallbladder emptying and pancreatic enzyme secretion. A maximal inhibition was attained by 1.5 microgram . min-1, and 0.05 microgram . min-1 somatostatin gave a significant 40% reduction. The inhibition persisted in the postinfusion period and was followed by delayed rebound outputs. The gallbladder emptying was completely arrested for variable periods of time, but the pancreatic enzyme secretion was never totally blocked. The promptly established arrest of the gallbladder differed from the slowly initiated inhibition of the gastric and intestinal propulsion. It is proposed that the multiple ways of action of somatostatin and different stimulatory levels contribute to the discrepancies. The study shows that somatostatin induces dose-dependent, long-lasting inhibitions of the biliary and pancreatic responses to oral glucose. The minimal effective dose was a hundred times lower than the dose tested in previous studies in man.

Release of somatostatin into the antral lumen of cats

Abstract Within the antral mucosa somatostatin is stored in cells that are morphologically similar to those that contain gastrin. 1 Furthermore, in anesthetized cats gastrin is released not only into the blood stream but also into the antral lumen. 2–4 For this reason, we have been searching for somatostatin in antral perfusates. In the present study we summarize data that show that somatostatin is released into the antral lumen of cats in response to certain stimuli.

Effect of Food Deprivation (Fasting) on Plasma Gastrin Levels in Man

We studied plasma gastrin levels in 12 healthy men before and after 4, 8 and 10 days of total food deprivation. The gastrin levels during the starvation period were significantly lower than the preexposure values. No such changes were observed in 6 other men, serving as controls, who were allowed to eat ad libitum during the experiment. Blood glucose levels and urinary output of catecholamines were measured concurrently. A pronounced hypoglycemia and a doubting of the urinary output of adrenaline were observed during the fasting period. Thus, depression of plasma gastrin concentrations occurs during starvation despite the presence of some potent gastrin-releasing factors, such as hypoglycemia and increased release of adrenaline. It is suggested that these depressions could be due to the absence of another potent stimulator of gastrin release, namely food in the stomach, or to neurogenic inhibition of gastrin release secondary to a stress-induced elevation of the sympathetic tone.

Phosphate Buffer Stimulates Somatostatin Release into the Antral Lumen of Anaesthetized Cats

The effect of variations of intra-antral pH on the intraluminal release of somatostatin was studied. Acute pouches were created in anaesthetized cats, and the pouches were perfused with solutions differing in pH. Somatostatin levels were then measured in the perfusates. In this model phosphate buffer was a potent stimulator of intra-antral somatostatin release, whereas perfusion with 0.1 M HCl failed to release somatostatin by itself. Since phosphate buffer also releases gastrin, the releasing effect ought to be exerted beyond the mechanism that can be blocked by somatostatin. (Thus the stimulatory effect of phosphate buffer might be exerted on the membranes of the endocrine cells.)

The Role of Catecholamines in the Control of Gastrin and Acid Secretion during Insulin Hypoglycaemia in Man

5 adrenalectomized subjects and 8 healthy volunteers underwent an insulin test during which acid secretion and plasma adrenaline, noradrenaline, dopamine and gastrin concentrations were measured. Plasma glucose concentration fell by greater than 50% in all subjects. The mean plasma adrenaline concentration increased markedly (greater than 1,000%) in the normal group but was unchanged in the adrenalectomized group. In all subjects, plasma noradrenaline concentration increased moderately, whereas plasma dopamine levels remained unchanged. Clear-cut increments in plasma gastrin concentration were seen only on 3 participants, each of whom responded to insulin hypoglycaemia with an extremely high adrenaline release. Basal and peak acid output were similar in adrenalectomized and normal subjects. The results suggest that circulating catecholamines contribute to the control of gastrin and acid secretion in man only during circumstances with high plasma catecholamine levels, e.g. severe stress.

EFFECT OF INTRALUMINAL pH ON THE RELEASE OF GASTRIN AND SOMATOSTATIN FROM THE ANTROPYLORIC REGION. THE POSSIBLE ROLE OF SOMATOSTATIN AS AN INHIBITORY HORMONE OF GASTRIC ACID SECRETION

Publisher Summary This chapter describes the effect of intraluminal pH on the release of gastrin and somatostatin from the antropyloric region. In experiments described in the chapter, the release of somatostatin in response to several intraluminal pH was studied in antral and bulbar perfusates of conscious dogs provided with chronic pouches of the antrum or duodenal bulb. In these experiments, it was found that low pH per se caused a release of somatostatin. The close anatomical relationship between the antral D-cell somatostatin and the G-cells containing gastrin indicate that the assumed inhibitory effect of somatostatin on gastrin release should be induced locally in the antral mucosa. It is proposed that both the inhibition of gastrin release and the release of gastric acid inhibitory hormones induced by antral and bulbar acidification are mediated by somatostatin released from the antrum and the duodenal bulb in response to low pH in this region. According to this hypothesis, the inhibition of stimulated gastrin release induced by acidification of the antrum is caused by local or paracrine effects exerted by the high levels of somatostatin occurring in the antral mucosa at this pH.