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 and on serum insulin and gastrin concentrations after ingestion of a mixed solid-liquid meal in humans

In a double-blind placebo-controlled study, we examined the effect of calcitonin on gastric emptying, and on serum concentrations of gastrin, insulin, glucose, calcium, and phosphorus after a mixed solid-liquid meal in 11 healthy men. Synthetic salmon calcitonin was administered as a 415 pmol i.v. bolus injection followed by a 90-min infusion to reach an overall dose of 62.25 pmol/kg body mass. Gastric emptying of a radiolabeled meal was surveyed by means of a gamma camera. A pronounced inhibition of gastric emptying with calcitonin was observed in all subjects (median gastric half emptying time 60.3 min after placebo versus 197.6 min after calcitonin; p less than 0.001). Calcitonin did not effect the postprandial gastrin release, nor did it change significantly the serum calcium or phosphorus concentrations. A decreased postprandial insulin release by calcitonin (mean +/- SEM area under the insulin curve 2,124.6 +/- 382.0 min mU L-1 after placebo versus 640.9 +/- 124.0 min mU L-1 after calcitonin; p less than 0.002) was accompanied by a different pattern of serum glucose concentrations during the infusion of the hormone when compared to the situation with a placebo. We discuss potential mechanisms and clinical relevance of our findings.     

Gastrin studies in gastric ulcer

Basal serum gastrin in 40 patients with benign gastric ulcer was 103 +/- 10.7 pg/ml, a level significantly higher than corresponding estimations in normal subjects and patients with duodenal ulcer.Following stimulation by a protein meal, a mean rise of 124 pg/ml was achieved at 75 minutes and prior atropinization induced a rise of 208 pg/ml at 90 minutes. Insulin hypoglycaemia produced a rise of 63 pg/ml which was not significantly changed with concomitant neutralization of gastric contents.These results suggest that patients with gastric ulcer have higher basal gastrin levels than normal and this is probably related to the lowered antral acidity. In addition, the protein meal and insulin hypoglycaemia responses suggest an increased antral G cell mass and the possibility of additional gastrin release from sites outside the antrum.It is doubtful whether the relative hypergastrinaemia has an aetiological role in gastric ulcer but it may have a role in the maintenance of gastric 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.     

Behaviour of acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids over six months from eradication of helicobacter pylori in duodenal ulcer patients. A controlled study.

The behaviour of basal and stimulated acid secretion, gastrin release, serum pepsinogen I, and gastric emptying of liquids was studied in 19 consecutive patients with Helicobacter pylori positive duodenal ulcer, over a follow up period of six months. Eleven patients were studied before and at three and six months after eradication with lansoprazole plus amoxicillin and tinidazole (case group), whereas the remainder, with persistent H pylori infection, were studied before and after three and six months from ulcer healing, thus constituting the control group. In the case group, three months after eradication, fasting serum pepsinogen I fell from (mean (SEM)) 91.9 (6.9) (pretreatment) to 72.2 (5.1) ng/l and the integrated gastrin response to a meal reduced from 11,470 (1174) (pretreatment) to 8130 (608) pg/ml/h (p < 0.05). Fasting serum gastrin concentrations and maximal acid output reduced significantly only six months after eradication. In contrast, no significant change of any of these measurements was seen in the control group either at three or six months from healing compared with the pretreatment values. Gastric emptying of liquids did not change over the entire period of follow up in both study groups. In conclusion, eradication of H pylori in duodenal ulcer patients is accompanied by a rapid fall in serum pepsinogen I and plasma gastrin concentrations, whereas a slight but significant reduction of maximal acid secretion takes place later on. In contrast, gastric emptying of liquids does not seem to be influenced by H pylori status.     

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.     

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study

BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses postoperative ileus. We present the results of a double blind, placebo controlled, crossover study of ghrelin in gastric emptying in patients with diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.     

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.     

Serum gastrin in duodenal ulcer: Part I Basal levels and effect of food and atropine

Fasting serum gastrin has been measured by radioimmunoassay in 72 patients with duodenal ulcer and compared with that in normals, patients with gastric ulcer, and with the Zollinger-Ellison syndrome. The mean (+/- SEM) gastrin levels were 15.7 +/- 1.5 pg/ml in the duodenal ulcer group, 32.1 +/- 4.3 pg/ml in normals, 118 +/- 18.1 pg/ml in gastric ulcer, and between 450 and 2,000 pg/ml in the Zollinger-Ellison syndrome. There were no difficulties in distinguishing simple ulcer from the Zollinger-Ellison syndrome as the presence of hyperchlorhydria in combination with hypergastrinaemia led to a confident diagnosis of the latter disease.The effect of protein, glucose, and cream feeding with and without atropine was also assessed in a group of these patients with duodenal ulcer. As in normals, there was no stimulation of gastrin release by either atropine alone, distilled water, glucose, or cream. However, protein alone produced a greater rise in serum gastrin levels compared with that in normals and prior atropinization augmented this response greatly in duodenal ulcer. This indicates an increased amount of releasable gastrin in the latter disease, the release of which, under basal conditions, is suppressed by the high acidity in the antrum.     

Serum gastric inhibitory polypeptide (GIP) in duodenal ulcer disease: relationship to glucose tolerance, insulin, and gastrin release

Serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG), and insulin (IRI) were estimated in 41 normal weight patients with duodenal ulcer (DU) and 25 age-matched controls in response to a high calorie liquid test meal. 28 out of 41 DU patients had a hyperglycaemic glucose response during the test meal, and 15 had a pathological oral glucose tolerance test. Fasting and food-stimulated IR-GIP and IRG levels were significantly elevated in the DU patients. Serum IRI also increased to significantly higher levels in DU patients after the test meal. The degree of the greater hormone response was dependent on the glucose increase after the test meal in the case of insulin and GIP, but not in the case of gastrin. It is concluded: firstly, that a faster glucose absorption (possibly due to rapid initial gastric emptying or increased intestinal motility) is responsible for the high and short-lasting glucose peak and the increased GIP and insulin secretion; secondly, that the GIP response could well be causally related to the insulin response; thirdly, that hyposcretion of GIP is ruled out as a possible factor in the pathogenesis of gastric acid hypersecretion of duodenal ulcer patients.     

Effect of placebo on meal-stimulated gastric acid secretion and serum gastrin concentration

The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion.     

Serum gastrin in duodenal ulcer: Part III Influence of vagotomy and pylorectomy

Following truncal vagotomy and anterior pylorectomy for duodenal ulcer, fasting serum gastrin levels were higher at 84 +/- 7.9 pg per ml than in unoperated patients with duodenal ulcer (16 +/- 1.5 pg per ml). In response to a standard protein meal, the peak serum gastrin achieved in the vagotomized group was 259 +/- 37.8 pg per ml at 75 minutes after ingestion, a much higher response than that obtained with a standard meal plus prior atropinization in the unoperated duodenal ulcer patients.These results suggest that truncal vagotomy allows release of gastrin which was previously inhibited with the vagi intact and the temporal characteristics of the response indicate that some of this gastrin is derived from an extragastric source. The results also exemplify the dependence of gastrin estimations as measured by this immunoassay on the acidity of the contents bathing the gastric antrum.     

Consequences of antral and duodenal acidification on acid secretion, gastrin response and gastric emptying in duodenal ulcer patients and normal subjects

The present study intended to investigate the effect of antroduodenal acidification on gastric acid secretion and emptying, gastrin and somatostatin release in response to food in healthy subjects as well as in duodenal ulcer patients. Ten duodenal ulcer patients and 9 normal controls were studied twice: the same 400 ml liquid protein meal (proteins: 10 g) was introduced into the stomach; then intragastric pH was either maintained at pH 4.5 or allowed to decrease in response to the meal. Acid secretion was calculated using the intragastric titration method (for which the intragastric pH is fixed at pH 4.5) and using the serial dilution indicator method (which allows antral acidification) respectively. Gastric emptying was estimated according to: a) iterative measurements of intragastric meal residual volume; b) volume passing through the pylorus. These two tests were performed in a random order and during each, plasma gastrin and somatostatin responses to the meal were determined. In healthy subjects, antral acidification following the meal was associated with a significantly lower acid secretion (17.3 +/- 0.9 mmol/h; m +/- SEM) than when the pH was maintained at pH 4.5 (20.2 +/- 1.3; p less than 0.05). Moreover, gastric emptying was slower when the pH was allowed to decrease (t 1/2: 26.2 +/- 1.4 min) than when the pH was constant (t 1/2: 20.5 +/- 2.2 min; p less than 0.05). By contrast, in the duodenal ulcer group, neither acid output nor gastric emptying were significantly different in the two situations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of bombesin on gastrin and gastric acid secretion in patients with duodenal ulcer

The effect of bombesin, a possible neurotransmitter of gastrin release, upon gastrin and gastric acid secretion was investigated in 25 patients with duodenal ulcer and in 16 normal subjects. In patients with duodenal ulcer bombesin (10 ng/kg/min) produced an increase in plasma gastrin output (median 22·4 (range 7·5-75·8) pmol/l/min) similar to that obtained in normal subjects (median 24·4 (range 5·8-56·5) pmol/l/min), whereas gastrin stimulated by a meal was significantly higher in the group of patients with duodenal ulcer (median 20·7 (range 9·2-42·9) vs 16·2 (range 3·4-22·2) p<0·05). Peak acid output induced by bombesin was significantly higher in patients with duodenal ulcer than in normal subjects (median 24·4 (range 9·0-63·8) vs 14·0 (range 3·0-24·8) mmol/h, p<0·05) despite identical gastrin outputs. The ratio (%) obtained by dividing the acid secretory response to bombesin by the response to pentagastrin, however, was similar in both normal subjects and patients with duodenal ulcer (median 55 (range 20-116) vs 58 (range 31-95) respectively). The difference between the gastrin response to food and bombesin could be explained by the fact that bombesin releases gastrin directly, whereas a protein meal involves several mechanisms (neural, peptidergic, paracrine, endocrine), either stimulatory or inhibitory. The above results indicate that a higher concentration in antral and/or duodenal gastrin is unlikely to be present in patients with duodenal ulcer. An increased parietal cell mass could explain the higher gastric acid response after bombesin infusion in our group of patients with duodenal ulcer.     

Bombesin and G-17 dose responses in duodenal ulcer and controls

Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: (1) an exaggerated release of gastrin with bombesin stimulation, and (2) a defective inhibition of acid and pepsin secretion with higher doses of bombesin.Presented at AGA, Washington, D.C., 1983.     

alpha-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7-36 amide) and to delay gastric emptying in Type 2 diabetic patients.

AIM: Acarbose is able to enhance GLP-1 release and delay gastric emptying in normal subjects. The effect of alpha-glucosidase inhibition on GLP-1 has been less evident in Type 2 diabetic patients. The aim of this study was to investigate the possible influence of acarbose on GLP-1 release and gastric emptying in Type 2 diabetic patients after a mixed test meal. PATIENTS AND METHODS: Ten Type 2 diabetic patients were tested with 100 mg acarbose or placebo served with a mixed meal that was labelled with 100 mg 13C-octanoic acid. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1 and GIP were determined over 6 h. Gastric emptying was measured by determining breath 13CO2 using infrared absorptiometry. Statistics repeated-measures anova. RESULTS: Gastric emptying rates (t1/2: 162 +/- 45 vs. 163 +/- 62 min, P = 0.65) and plasma concentrations (increasing from approximately 12 to approximately 25 pmol/l, P = 0.37) and integrated responses of GLP-1 (P = 0.37) were not changed significantly by acarbose treatment. Postprandial plasma glucose concentrations (P < 0.0001) and their integrated responses were lowered by acarbose (by 64%; P = 0.016). The plasma concentrations of insulin and C-peptide were reduced (P = 0.007 and 0.057, respectively) by acarbose, while glucagon was not changed (P = 0.96). GIP plasma concentrations (increasing with placebo from approximately 10 to approximately 85 pmol/l and with acarbose to approximately 55 pmol/l (P < 0.0001) and their integrated responses were significantly lowered (by 43%) by acarbose (P = 0.021). After 2 weeks of acarbose treatment (50 mg t.i.d. for the first and 100 mg t.i.d. for the second week, n = 6), similar results were found. CONCLUSIONS: In hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a mixed test meal failed to enhance GLP-1 release and did not influence gastric emptying.     

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.     

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.     

Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM

Summary Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were studied twice in a randomised, double-blind crossover design. Euglycaemia was maintained overnight by intravenous infusion of glucose and/or insulin and the following morning a 5-h infusion of pramlintide 25 μg/h or placebo was started at 08.00 hours. At 08.30 hours the patients injected their normal morning insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50 % carbohydrate) of which the solid component was labelled with Technetium-99 m and the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic images were obtained every 20 min for the next 4 h. Insulin and glucose were infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre-meal value. Compared to placebo, pramlintide significantly delayed emptying of both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs 44.5 min) components of the meal. Pramlintide delayed gastric emptying so much that t₅₀ values could not be calculated for solid or liquid. Amylin agonists such as pramlintide may, therefore, be of value in improving glycaemic control in IDDM by modifying gastric emptying. [Diabetologia (1997) 40: 82–88] Received: 22 March 1996 and in revised form: 24 September 1996     

A synthetic prostaglandin E2 analogue, enprostil, hastens gastric emptying of solids in patients with an active duodenal ulcer

The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.