Effect of calcitonin on gastric emptying and on postprandial gastrin and insulin release in patients with type I gastric ulcer

In a double-blind placebo-controlled study, the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in six patients with type I gastric ulcer. Synthetic salmon calcitonin 415 pmol i.v. was given as a bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin suppressed gastric emptying in all patients examined. The mean gastric transit time, MTT90, increased from 38.1 +/- 0.4 min after placebo to 43.1 +/- 0.6 min after calcitonin (P less than 0.001). Calcitonin significantly blunted the postprandial gastrin release: AUC0-90 10,398 +/- 2886 ng. l-1 min (placebo) and 8238 +/- 2573 ng. l-1 min (calcitonin), P less than 0.05, and abolished the postprandial insulin release--AUC0-90 2244 +/- 230 mU.l-1 min (placebo) vs. 638 +/- 198 mU.l-1 min (calcitonin), P less than 0.01. A steady increase in the serum glucose during calcitonin infusion, reaching up to 5.6 +/- 0.31 mmol.l-1 at the end of the infusion, was observed. Calcitonin did not significantly affect serum calcium or phosphorus concentrations. The authors conclude that a delayed gastric emptying is to be expected in patients undergoing calcitonin treatment.     

Effect of calcitonin on gastric emptying in patients with an active duodenal ulcer.

In a double blind placebo controlled study the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in eight patients with duodenal ulcer. Synthetic salmon calcitonin 415 pmol iv was given as a bolus followed by a 90 minute infusion to reach an overall dose of 62.25 pmol/kg. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin markedly delayed gastric emptying in all patients examined. The emptying index (Ix) decreased from 2.979 (0.397)/min after placebo to 0.896 (0.317)/min after calcitonin (p less than 0.001). Calcitonin did not affect significantly postprandial gastrin release: AUC0-90, 8768 (880) pg/l min (placebo) and 7807 (619) pg/l min (calcitonin). Postprandial insulin release was abolished by calcitonin -Auc0-90, 2258 (242) mU/l min (placebo) v 736 (131) mU/l min (calcitonin), p less than 0.001. Parallel to the suppression of insulin release was a steady increase in the serum glucose during calcitonin infusion, with the highest glucose concentration of 5.8 (0.53) mmol/l at the end of infusion of the hormone. Calcitonin did not change significantly serum calcium or phosphorus concentrations. A combination of a delaying effect on gastric emptying with the inhibition of gastric acid secretion elicited by calcitonin warrants further studies of calcinonin in the treatment of duodenal ulcer.     

Effect of calcitonin on gastric emptying

The effect on gastric emptying of synthetic salmon calcitonin administered intravenously (415 pmol bolus injection followed by infusion to reach an overall dose of 62.25 pmol.kg-1 body mass) versus placebo was examined in 13 healthy men. Gastric emptying of a radiolabeled solid meal was assessed with a gamma camera. The gastric emptying course was analyzed with the use of the power-exponential fitting. A marked delay in gastric emptying was observed in all subjects studied: the median gastric half emptying time was 60.3 min after placebo and 196.5 min after calcitonin (p less than 0.001). At the same time, analysis of the parameter S revealed that calcitonin did not elicit any consistent change in the shape of gastric emptying curves.     

Effect of loxiglumide on basal and gastrin- and bombesin-stimulated gastric acid and serum gastrin levels.

The effect of the specific cholecystokinin-receptor antagonist loxiglumide on basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg.kg-1.h-1) significantly augmented basal gastric acid output from 1.8 +/- 0.3 to 3.9 +/- 0.6 mmol H+/h (P less than 0.005) but did not significantly influence integrated basal serum gastrin concentrations (2 +/- 21 vs. 32 +/- 21 pmol L-1.h-1). Both gastric acid secretion and integrated serum gastrin concentrations stimulated by bombesin infusion (92.6 pmol.kg-1.h-1) were significantly augmented by loxiglumide [from 4.0 +/- 0.3 to 10.0 +/- 1.3 mmol H+/h (P less than 0.005) and from 1251 +/- 93 to 2558 +/- 206 pmol.L-1.h-1 (P less than 0.005), respectively]. Gastric acid output and serum gastrin concentrations during infusion of 5 pmol.kg-1.h-1 of synthetic human gastrin 17-I (9.6 +/- 2.9 mmol H+/h and 1045 +/- 177 pmol.L-1.h-1) and during infusion of 15 pmol.kg-1.h-1 of gastrin 17-I (14.5 +/- 3.1 mmol H+/h and 2412 +/- 312 pmol.L-1.h-1) were not significantly influenced by loxiglumide (10.3 +/- 2.3 mmol H+/h and 1291 +/- 257 pmol.L-1.h-1 for the 5-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide and 13.6 +/- 3.4 mmol H+/h and 2611 +/- 305 pmol.L-1.h-1 for the 15-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide). These data indicate that endogenous cholecystokinin inhibits gastric acid secretion under basal conditions and gastrin release and gastric acid secretion during infusion of bombesin in humans and suggest that the augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may be explained largely by enhanced gastrin release.     

A role for pancreatic polypeptide in the regulation of gastric emptying and short-term metabolic control

CONTEXT: Previous studies using pancreatic polypeptide (PP) infusions in humans have failed to show an effect on gastric emptying, glucose metabolism, and insulin secretion. This might be due to the use of nonhuman sequences of the peptide. OBJECTIVE: The objective of this study was to use synthetic human PP to study gastric emptying rates of a solid meal and postprandial hormone secretion and glucose disposal as well as the gastric emptying rate of water. DESIGN: This was a single-blind study. SETTING: The study was performed at a university hospital. PARTICIPANTS: Fourteen healthy adult subjects were studied. Interventions: Infusion of saline or PP at 0.75 or 2.25 pmol/kg.min was given to eight subjects (gastric emptying of solid food), and infusion of saline or PP at 2.25 pmol/kg.min was given to six subjects (gastric emptying of water). MAIN OUTCOME MEASURES: The main outcome measures were gastric emptying of solids (scintigraphy), hunger ratings (visual analog scale), and plasma concentrations of PP, insulin, glucagon, somatostatin, glucagon-like peptide 1, glucose, and gastric emptying of plain water (scintigraphy). RESULTS: PP prolonged the lag phase and the half-time of emptying of the solid meal. The change in hunger rating, satiety, desire to eat after the meal, or prospective consumption was not affected. The postprandial rise in plasma glucose was prolonged by PP. The postprandial rise in insulin was also delayed by PP. PP had no significant effect on the emptying of water. CONCLUSIONS: PP inhibits gastric emptying of solid food and delays the postprandial rise in plasma glucose and insulin. PP is suggested to have a physiological role in the pancreatic postprandial counterregulation of gastric emptying and insulin secretion.     

Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.     

Physiological role of cholecystokinin on gastric emptying and acid output in dogs

We investigated the physiological role of cholecystokinin (CCK) on gastric emptying and acid secretion in seven conscious dogs with gastric cannulae. Two hundred milliliters of a 4% amino acid meal was given via the cannula, and both gastric emptying and acid output were measured concurrently using a dye-dilution technique. Gastric emptying of the liquid amino acid meal was exponential, and the acid output and plasma concentrations of CCK, gastrin, and somatostatin peaked within 30 min after the meal. Intravenous infusion of CCK-8 at 28 and 56 pmol/kg/hr but not 14 pmol/kg/hr increased plasma levels of the peptide and inhibited gastric emptying as well as acid output. Plasma gastrin was not affected significantly by the CCK infusion, whereas plasma somatostatin increased significantly in response to 56 pmol/kg/hr of CCK-8. Loxiglumide, 22 µmol/kg/hr, significantly enhanced gastric emptying and augmented acid output, as well as plasma gastrin response, whereas it abolished the postprandial rise in plasma somatostain. We concluded that in dogs, CCK plays an important role in the physiologic regulation of postprandial gastric emptying of a liquid caloric meal and acid output. Its inhibitory effect on gastric acid secretion appears to be mediated, at least in part, by somatostatin.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Science.The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, HHS/NIH, Publ. No. 85-23.     

Glucagon-like peptide 1 abolishes the postprandial rise in triglyceride concentrations and lowers levels of non-esterified fatty acids in humans

Aims/hypothesis Diabetic dyslipidaemia contributes to the excess morbidity and mortality in patients with type 2 diabetes. Exogenous glucagon-like peptide 1 (GLP-1) lowers postprandial glycaemia predominantly by slowing gastric emptying. Therefore, the effects of GLP-1 on postprandial lipid levels and gastric emptying were assessed. Methods 14 healthy male volunteers were studied with an i.v. infusion of GLP-1 (1.2 pmol kg⁻¹ min⁻¹) or placebo over 390 min in the fasting state. A solid test meal was served and gastric emptying was determined using a ¹³C-labelled sodium octanoate breath test. Venous blood was drawn frequently for measurement of glucose, insulin, C-peptide, glucagon, GLP-1, triglycerides and NEFA. Results GLP-1 administration lowered fasting and postprandial glycaemia (p<0.0001). Gastric emptying was delayed by GLP-1 compared with placebo (p<0.0001). During GLP-1 administration, insulin secretory responses were higher in the fasting state but lower after meal ingestion. After meal ingestion, triglyceride plasma levels increased by 0.33±0.14 mmol/l in the placebo experiments (p<0.0001). In contrast, the postprandial increase in triglyceride levels was completely abolished by GLP-1 (change in triglycerides, −0.023±0.045 mmol/l; p<0.05). During GLP-1 infusion, plasma concentrations of NEFA were suppressed by 39% in the fasting state (p<0.01) and by 31±5% after meal ingestion (p<0.01). Conclusions/interpretation GLP-1 improves postprandial lipidaemia, presumably as a result of delayed gastric emptying and insulin-mediated inhibition of lipolysis. Thus, by lowering both glucose and lipid concentrations, GLP-1 administration may reduce the cardiovascular risk in patients with type 2 diabetes.     

Effect of altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic patients

The purpose of this study was to determine the effects of altering gastric emptying on postprandial plasma glucose concentration after a physiologic meal in patients with type II diabetes mellitus (T II DM). Nine T II DM patients underwent a double-blind, randomized, three-way crossover study, receiving erythromycin 200 mg, morphine 8 mg, or normal saline (placebo) intravenously prior to ingestion of a radiolabeled, dual-isotope, solid–liquid meal. Gastric emptying of solids and liquids and serial plasma glucose, glucagon, and serum insulin concentrations were measured at baseline and for 5 hr after meal ingestion. Erythromycin accelerated and morphine delayed solid- and liquid-phase gastric emptying compared to placebo (P < 0.05). During the first hour, the postprandial plasma glucose concentrations were higher after erythromycin (P < 0.05) and lower after morphine (P < 0.05) compared to placebo. The peak postprandial plasma glucose concentration was higher after erythromycin (P = 0.05) and lower after morphine (P < 0.05) compared to placebo. In conclusion, pharmacologic acceleration of gastric emptying resulted in higher postprandial glucose concentrations, while delaying gastric emptying resulted in lower postprandial glucose concentrations after a physiologic meal in T II DM. These results suggest that administration of opiate analgesics or prokinetic agents to diabetic patients may alter glucose control. Modifying gastric emptying may be helpful in achieving glucose control in T II DM.     

Truncated GLP-1 (proglucagon 78–107-amide) inhibits gastric and pancreatic functions in man

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78–107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110±14 pmol/liter (mean±SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43±11%, in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16±2 min to 30±5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47±17% and 40±9%, during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 ±0.2 versus 3.7±0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.This work was supported by the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faroe Islands and Greenland; the Danish Medical Research Council, and the Novo Foundation     

Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide

Summary Cholecystokinin was previously proposed to play an important role in the regulation of postprandial insulin secretion either indirectly, by inhibiting gastric meal emptying, or directly, by acting as an incretin promoting the release of insulin. The aim of this investigation was therefore to clarify the role of endogenous cholecystokinin in the regulation of insulin release and gastric emptying applying the highly potent and specific cholecystokinin receptor antagonist loxiglumide. Five healthy volunteers were examined after an overnight fast. Gastric meal emptying was measured by the double indicator technique using a multiple lumen tube in the duodenum and ^99mTc-diethylenetriamine pentaacetate as a meal marker and polyethylene glycol 4000 as a duodenal perfusion marker. Postprandial insulin, C-peptide, cholecystokinin and glucose levels were measured after ingestion of two isocaloric meals of a) Ensure (containing fat, protein and glucose), and b) a pure glucose meal (1.11 mol/l). The meals were given either with an intravenous infusion of loxiglumide (22 mol·kg^–1·h^–1) or placebo. The infusion of loxiglumide markedly accelerated the gastric emptying of the mixed meal (area under curve, 5576±352 min vs 3498±109 min; p<0.001) and the pure glucose meal (area under curve 5662±537 min vs 3551±534 min; p<0.05). Simultaneously, loxiglumide induced a more rapid rise in postprandial insulin levels after both meals resulting in significantly higher (p<0.05) insulin levels during the first postprandial hour, but similar insulin levels in the second postprandial hour. Accordingly, we found a close correlation between meal emptying and insulin release (r=0.748, p<0.01). Integrated insulin and C-peptide levels for the whole 2-h experimental period tended to be higher during loxiglumide infusion, but the difference did not reach statistical significance. Similar plasma glucose levels at all time periods were observed with and without loxiglumide infusion. Higher cholecystokinin levels were measured during loxiglumide infusion after the mixed (p<0.01) and the pure dextrose (p<0.05) meals. We conclude that postprandially released cholecystokinin exerts an important role in the regulation of gastric meal emptying and consecutively the postprandial pattern of insulin release. In contrast, no evidence was found for an insulinotropic role for cholecystokinin in man.     

Opposite effects of bombesin on insulin and gastrin response to food in humans.

The effect of bombesin on insulin and gastrin response to a standard labelled meal was studied in eight healthy male volunteers. The gastric emptying of solids was simultaneously evaluated. During intravenous infusion of the peptide (5 ng/kg/min) the insulin release after eating was greatly reduced whereas food stimulated gastrin release was significantly enhanced. Both effects of bombesin are likely to be connected with the marked inhibition of gastric emptying induced by the peptide.     

Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes

The effects of different i.v. doses of glucagon-like peptide 1 (GLP-1) on glucose homeostasis and gastric emptying were compared in patients with type 2 diabetes. Twelve patients with type 2 diabetes received three different infusion rates of GLP-1 (0.4, 0.8, and 1.2 pmol/kg x min) or placebo in the fasting state and after a solid test meal (containing [(13)C]octanoic acid). Blood was drawn for glucose, insulin, C-peptide, glucagon, and GLP-1 determinations. The gastric emptying rate was calculated from the (13)CO(2) excretion rates in breath samples. Statistics were determined using repeated measures ANOVA and Duncan's post hoc test. Plasma glucose concentrations were equally normalized with all GLP-1 doses (P < 0.001). Insulin and C-peptide concentrations dose-dependently rose during GLP-1 infusion in the fasting state (P < 0.05), but were dose-dependently reduced by GLP-1 after meal ingestion (P = 0.0031 and 0.0074, respectively). Glucagon secretion was suppressed with GLP-1. Gastric emptying was decelerated by GLP-1 in a dose-dependent fashion (P < 0.001). Despite a dose-dependent stimulation of insulin secretion, glucose normalization can be achieved even with 0.4 pmol GLP-1/kg x min. Due to the dose-dependent inhibition of gastric emptying, lower GLP-1 doses than previously used may be as suitable for glucose control in patients with type 2 diabetes.     

Differences in pharmacokinetics and pharmacodynamics of insulin lispro and aspart in healthy volunteers.

Pharmacokinetic and pharmacodynamic profiles of the rapid-acting insulin analogues lispro and aspart were compared in a randomized, double-blind crossover study of 20 fasting healthy men following a single subcutaneous injection. Either insulin lispro or aspart, 0.05 U/kg-body-weight, was injected subcutaneously and followed by determination of 5-h profiles of plasma glucose, serum C-peptide and insulin concentrations. Lowest glucose concentrations were observed after 50 min in the aspart group (3.2 +/- 0.1 mmol/l versus lispro 3.5 +/- 0.1 mmol/l; p = 0.026) and after 60 min in the lispro group (3.4 +/- 0.1 mmol/l). For blood glucose t min was 59.3 +/- 3.4 min in the aspart and 63.5 +/- 5.3 min in the lispro group (ns). After 40 min a lower C-peptide was determined for aspart (225 +/- 21 pmol/l versus lispro 309 +/- 33 pmol/l; p = 0.031), whereas minimal C-peptide concentrations were reached in both groups after 105 min (lispro 117 +/- 21 pmol/l versus aspart 105 +/- 18 pmol/l). The maximal concentration of insulin was detected in both groups after 40 min (lispro 20.8 +/- 1.1 mU/l versus aspart 24.6 +/- 1.3 mU/l; p = 0.032). For insulin t max was 33.0 +/- 2.6 min in the aspart versus 33.3 +/- 2.6 min in the lispro group (ns). The present results indicate a more rapid absorption of insulin aspart in comparison to insulin lispro. Higher insulin concentrations after subcutaneus injection may be advantageous in meal-related treatment of diabetes.     

Variable contribution of gastrin to gastric acid secretion after a meal in humans

The purpose of these experiments was to determine the contribution of gastrin to the acid secretory response to eating in healthy human subjects. To simulate the gastric and intestinal phases of eating, a meal was homogenized and then infused into the stomach through a nasogastric tube. At the same time, the cephalic phase of acid secretion was activated by sham feeding. With this simulated meal, mean serum gastrin concentration increased from a basal value of 43 +/- 9 pg/ml to an average postprandial gastrin concentration over 2 h of 121 +/- 25 pg/ml. Gastrin release after this simulated meal was similar to gastrin release after a normally eaten meal in the same 12 subjects. Gastric acid secretion in response to the simulated meal, which was measured by in vivo intragastric titration, averaged 24.2 +/- 2.4 mmol/h. To determine how much of this postprandial acid secretion could be attributed to gastrin, gastrin 17 I was infused intravenously in the same subjects on a separate day and acid secretion and serum gastrin concentrations were measured. By relating serum gastrin concentration during gastrin 17 infusion to concomitant acid secretion, we determined that an average postprandial serum gastrin concentration of 121 pg/ml could result in an acid secretion rate of 21.5 mmol/h, 89% of the actual acid secreted after the simulated meal in these subjects. However, in individual subjects, the amount of gastrin released after a meal could produce as little as 51% or as much as 162% of actual postprandial acid secretion. Thus, in individual human subjects the contribution of gastrin to acid secretion after a meal is variable.     

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.     

Effect of calcitonin on gall-bladder volume in man

The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.     

The influence of the migrating motor complex on the postprandial endocrine response

BACKGROUND: The phase of the migrating motor complex (MMC) in the proximal small intestine at meal intake modulates gastric emptying, which is accelerated after intake during phase II. In the present study the relationship between phase of the MMC at meal intake and the postprandial endocrine response was studied. METHODS: Eight healthy subjects ingested a caloric liquid meal of 2020 kJ during phase I and late phase II of the intestinal MMC, respectively, in a randomized order. Blood samples were drawn at regular intervals after meal intake and analysed for insulin, gastrin, neurotensin, cholecystokinin, motilin, and somatostatin by radioimmunoassays. RESULTS: The area under the curve (AUC) until 15 min for serum insulin (P<0.05) and plasma neurotensin (P<0.02) and AUC until 120 min for serum gastrin (P<0.05) were higher after intake during late phase II than after phase I. Plasma cholecystokinin increased earlier (P<0.05) after intake during late phase II than after phase I. Plasma motilin and somatostatin were not influenced by preceding phase of the MMC. CONCLUSIONS: This study shows that the phase of intestinal MMC at meal intake modulates the postprandial endocrine response, which may be explained by the prior entry of nutrients to the small intestine after intake during phase II.     

A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the beta cell response or glucose tolerance in type 2 diabetes mellitus

Newly diagnosed, previously untreated patients with type 2 diabetes mellitus (n = 6) were studied on two separate days after overnight fasts. On each day they were given a 500-kcal mixed meal plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (GIP) (0.75 pmol/kg/min) or control solution (CS) from 0 to 30 min in random order. Frequent measurements of plasma glucose, C-peptide, insulin and GIP concentrations were made. Fasting GIP levels were similar on both days. During the meal plus GIP infusion plasma GIP levels increased from a basal value of 7.6 +/- 1.5 pmol/1 to a peak of 88.6 +/- 5.4 pmol/1 at 30 min. Following the meal infusion of CS GIP increased from a fasting level of 10.3 +/- 1.2 pmol/1 to a significantly lower peak of 58.0 +/- 8.3 pmol/1 at 60 min. During the meal plus GIP infusion GIP levels were higher at 10-45 min and at 90 min (P less than 0.05-0.001). Fasting and postprandial glucose, C-peptide and insulin levels were, however, similar on both study day. A supplementary infusion of porcine GIP with a mixed meal did not significantly alter the beta cell response or glucose tolerance in this group of patients with type 2 diabetes mellitus.     

Effect of cimetidine on serum gastrin and gastric emptying in man.

Paired studies of gastric emptying were performed in 10 healthy volunteers using a scintiscanning technique which provides information about the rate of emptying of both the liquid and solid components of a standard meal. Emptying rates of both components were not significantly different after oral administration of 400 mg cimetidine than after placebo. The increase in serum gastrin concentration produced by the meal was significantly greater after cimetidine than after placebo but there was no relationship between individual cimetidine-placebo differences in gastrin response and the corresponding cimetidine-placebo differences in rates of emptying. A positive correlation was demonstrated between the gastric emptying rate of the liquid component and the 1 h cimetidine absorption, indicating that normal individual variation in gastric emptying is probably responsible for much of the normal individual variation in the rate of cimetidine absorption.