Relationship of satiety to postprandial glycaemic, insulin and cholecystokinin responses.

The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin (CCK) remain unclear. The aim of this study was to test the hypothesis that the magnitude of the postprandial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety. Seven healthy, male volunteers consumed equal carbohydrate portions (0.5 g/kg body weight) of six test meals (Rice Bubbles, Sustain, Vita-Brits, All-Bran, porridge and white bread) in random order after an overnight fast. An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight. Serum CCK, plasma glucose and insulin and subjective satiety (measured by a rating scale) were assessed over 3 h and quantified using the glycaemic index (GI), insulin index (II), the peak satiety score and area under the incremental curve (AUC). The observed GIs (mean +/- SE) ranged from 42.5 +/- 2.6 for All-Bran to 116.2 +/- 11.4 for Rice Bubbles, using white bread as the reference food (GI = 100). Peak satiety scores varied eightfold from 0.21 +/- 0.4 for Sustain to 1.64 +/- 0.4 for All-Bran. Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals (r = -0.916, p less than 0.001 and r = -0.926, p less than 0.001). A direct relationship was observed between satiety (AUC) and the CCK response (AUC) (r = 0.73 p less than 0.01). The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety.

Effects of bombesin antagonists on the growth of small cell lung cancer cells in vitro.

Small cell lung cancer (SCLC) produces several neuroendocrine peptides, including gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin. There is some evidence to support the suggestion that GRP is an autocrine regulator of SCLC growth. Therefore, we have tested the effect of bombesin and two antagonists of bombesin on SCLC cell growth in a serum-free liquid tissue culture system. The antagonists used were analogues of substance P: spantide and (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P. The cell lines used in this study all produced GRP-related peptides and one line had demonstrable GRP receptors. Exogenous bombesin did not cause any stimulation of growth in the liquid culture assay. The bombesin antagonists inhibited SCLC cell growth, but apparently not via the bombesin receptor. The bombesin used was biologically active because it stimulated the proliferation of Swiss 3T3 fibroblasts. The antagonists caused inhibition of this bombesin-induced proliferation, which was reversed by addition of excess bombesin. In addition, the antagonists and substance P alone stimulated proliferation of 3T3 cells, indicating that they may interact with another growth factor receptor on 3T3 cells. We conclude that growth of SCLC cells is not dependent on bombesin under all in vitro culture conditions because bombesin failed to stimulate growth in liquid cultures and the growth inhibition caused by bombesin antagonists was probably not mediated by the bombesin receptor.

Comparative effects of bombesin and porcine gastrin-releasing peptide in the dog.

Bombesin and porcine gastrin-releasing peptide (GRP) share a common C-terminal decapeptide fragment and are known to have similar bioactivity. The potencies of parenterally administered GRP and bombesin have been compared in their effects on gastric acid output, serum gastrin, and serum pancreatic polypeptide. In the dose range 0-720 pmol/kg/hr, infusions of both peptides resulted in dose-related increases of gastric acid output and corresponding elevations of serum gastrin and pancreatic polypeptide. At the dose of 1440 pmol/kg/hr, both bombesin and GRP resulted in a decrease in gastric acid output and serum gastrin. The mechanism of this inhibition is unknown. No significant difference in potency between the two peptides in changing gastric acid output, serum gastrin, and pancreatic polypeptide was observed. The demonstration of equimolar potency of porcine GRP and bombesin support the concept that GRP is mammalian bombesin.

Distribution of bombesin- and cholecystokinin-like immunoreactivity in rat and dog brain and gastrointestinal tract.

Using a specific bombesin radioimmunoassay and an immunoassay for cholecystokinin which sees all C-terminal fractions, the distribution of bombesin-like (BLI) and cholecystokinin-like (CCK-LI) immunoreactivity in the brain and gastrointestinal tract of the rat and dog has been studied. Both peptides are found in the brain and gut but the rat contains more CCK and BLI than the dog; this is particularly noted in the stomach, colon and cerebral cortex whereas the small intestine of both species contains equivalent amounts of peptides. This contrasts with other comparative studies, mainly on nervous system CCK, which find no major distribution differences in man, monkey, pig and rat. This finding suggests that CCK-LI and BLI peptides may have a more predominant role in the rat than in the dog.

Bombesin-like immunoreactivity in rat brain and gastrointestinal tract: influence of diet and starvation.

A radioimmunoassay has been developed for the measurement of bombesin-like immunoreactivity (BLI) in mammalian tissues. BLI has been demonstrated in large amounts in the rat stomach and colon and in smaller amounts in the rat central nervous system. A 7-day high-carbohydrate diet leads to an increase in gastric and colonic BLI, a high protein diet to a decrease in fundic BLI. High fat and protein diets led to a decrease in midbrain BLI but other nervous tissues were not influenced by variation in diet. A 6-day fast increased antral, jejunal and ileal BLI; these increased levels fell on refeeding. These studies suggest a role for endogenous BLI in some aspects of gastric physiology, perhaps gastrin release.

The effect of glucagon on serum gastrin. I. Studies in normal subjects.

Serum gastrin has been determined by radioimmunoassay in 13 subjects free of gastrointestinal disease, in the basal state, and following the intravenous injection of 1 mg glucagon. Serum gastrin fell from a mean +/- SEM level of 50.3 +/- 6.7 to 9.4 +/- 3.3 pg/ml at 30 minutes after injection, significant at p<0.005. This is similar to the response previously reported for secretin and indicates a role for glucagon in the control of gastrin release.

Effect of glucagon on serum gastrin. II. Studies in pernicious anaemia and the Zollinger-Ellison syndrome.

Serum gastrin was measured by radioimmunoassay in four patients with pernicious anaemia and four patients with the Zollinger-Ellison syndrome before and after the intravenous injection of 1 mg glucagon. Serum gastrin fell significantly in the patients with pernicious anaemia whilst in the patients with the Zollinger-Ellison syndrome there was a significant rise. Concomitant measurement of gastric acid output in one subject with the Zollinger-Ellison syndrome also showed a rise in acid output with glucagon. The reason for the paradoxical rise in gastrin in response to glucagon in the Zollinger-Ellison syndrome is unknown, but the response may provide a further diagnostic aid to this condition.

Extragastric gastrin.

Gastrin release in the basal state and following a standard protein meal has been estimated in patients after partial gastrectomy, partial gastrectomy with truncal vagotomy, and total gastrectomy. Following partial gastrectomy, gastrin rose from 8 +/- 0.8 to 20 +/- 3.8 pg/ml with a protein meal. The rise in the partial gastrectomy with truncal vagotomy group was 27 +/- 0.8 to 92 +/- 1.5 pg/ml and after total gastrectomy was 13 +/- 1.5 to 58 +/- 4.6 pg/ml. These results provide evidence for the release of gastrin from extragastric sites.

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.

Serum gastrin in duodenal ulcer. 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.

Effect of food on serum gastrin evaluated by radioimmunoassay.

The effect of food on serum gastrin in normal man has been evaluated by radioimmunoassay. Protein and amino acids produced up to a five-fold increase in serum gastrin levels, followed in potency by alcohol, fat, and glucose. Distilled water did not stimulate the release of gastrin. An injection of atropine sulphate (0.6 mg) augmented the response to all good stimuli but in itself did not affect serum gastrin levels in the basal state.

Radioimmunoassay of gastrin: studies in pernicious anaemia.

Serum gastrin levels in patients with pernicious anaemia were measured by immunoassay in the fasting state, following gastric perfusion with 0.9% saline, 0.1N hydrochloric acid, and solutions of increasing acidity, and after the intravenous injection or infusion of secretin. The fasting serum gastrin level was measured in 21 patients with pernicious anaemia and found to be elevated at 1,036 +/- 215 pg per ml. Gastric perfusion with saline (pH 4.7) caused a mean fall in serum gastrin of 30% in four patients; perfusion with hydrochloric acid caused a further slight fall. Perfusion with solutions of increasing acidity resulted in a sharp fall in serum gastrin levels when the acidity was changed from pH 6 to pH 4. A single intravenous injection of secretin produced a mean maximal fall of 44% in the serum gastrin level in four patients, whereas continuous infusion of secretin produced a fall of 35% in four other patients. These studies suggest that the gastrin-secreting cells of the stomach are not affected by the atrophic process in pernicious anaemia and remain subject to the regulating control of acid and secretin.