Susan M. Wood

Effect of long acting somatostatin-analogue, SMS 201995, on gut hormone secretion in normal subjects

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s. c. injection of 50 μg it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.

Impaired growth hormone response to human pancreatic growth hormone releasing factor [GRF(1-44)] in type 2 (non-insulin-dependent) diabetes.

SummaryHuman pancreatic growth hormone releasing factor [GRF(1–44)] is the largest molecule of several peptides recently isolated from pancreatic tumours associated with acromegaly. It has been shown to stimulate the release of growth hormone in normal subjects and provides a safe and reliable tool for examining growth hormone release. A study was conducted to examine the release of growth hormone in patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes. GRF(1–44) stimulated the release of growth hormone in normal subjects and produced no side effects. A response of similar magnitude occurred in Type 1 diabetic patients despite their concomitant hyperglycaemia. In contrast, the response in Type 2 diabetes was significantly impaired compared with normal volunteers (p<0.05) and Type 1 diabetic patients (p<0.02). These findings may well indicate that there is a defect in central hormonal control in Type 2 diabetes.

Distribution of Gut Peptides and Their Actions

Secretin was the first peptide to be identified within the gastrointestinal tract, and provided the prototype for the classical hormones, in that it is released by acid from endocrine cells in the duodenum and passes via the circulation to its effector organ, the exocrine pancreas1. The discovery of gastrin was soon to follow, but it was some twenty years later before further active components were identified from gut extracts. The major limitation of these studies,which showed that intravenous gut extracts could mimic the biological actions normally induced by enteric stimuli,such as acid or food, was the inability at that time to isolate the active substances from the crude extracts. It was not until the 1960s that the techniques of purification and structural analysis pioneered by Gregory and Mutt, allowed investigation of the active substances extracted from the gut, to advance3,4, Many of the classical hormones and a continuing stream of new peptides have now been purified and sequenced by these methods 5,6.

The Entero-Insular Axis

Although circulating glucose is the prime regulator of insulin secretion, it is unlikely that the insulin rise occurring in response to a meal is mediated solely by a change in the glucose concentration bathing the B cell. If this were the case one would expect to observe a large rise in plasma glucose followed by a rise in insulin, such a delay in the insulin response would be unlikely to maintain glucose homeostatis. In practice plasma glucose and insulin rise in parallel, suggesting a mechanism whereby insulin requirements are anticipated by the B cell, resulting in appropriate insulin secretion to hold the postprandial glucose rise within narrow limits. The most logical site for such a regulatory mechanism would seem to be the gut. The first appreciation of gut regulation of the pancreas began as early as 1902 when Bayliss and Starling introduced the concept of ‘chemical regulation’. At that time they showed that the intravenous injection of an extract of intestinal mucosa stimulated pancreatic exocrine secretion in the dog to the same extent as acid placed in the gut; and acid produced the same effect even when all neural connections between gut and pancreas were cut.1 The chemical messenger within these extracts was of course secretin, which was not to be isolated until 1952.2

Pancreatic and Gastrointestinal Hormone-Secreting Tumors

Publisher Summary This chapter discusses the pancreatic and gastrointestinal hormone-secreting tumors. The endocrine tumors of the gut have been linked together because of their common derivation from cells with amine precursor uptake and decarboxylation characteristics. Such cells have similar ultrastructural and cytochemical features and possibly a common embryological origin. A glycolytic enzyme, neuron-specific enolase, has recently been found to be present in these cells and is likely to be a further useful marker of neuroendocrine cells and their tumors. These tumors, apart from the carcinoids, are found most commonly in the pancreas. The peptides they secrete are the normal products of the cells of the islets of Langerhans—the A, B, D, and PP cells, which contain glucagon, insulin, somatostatin, and pancreatic polypeptide, respectively.

44 – Pancreatic Tumors

Publisher Summary This chapter describes tests to diagnose pancreatic tumors. Insulin tolerance tests are used to demonstrate failure of insulin suppression diagnostic of these tumors only when fasting has not done so. Hypoglycemia is induced either by fish insulin, which is biologically active but does not crossreact with the human insulin assay, or by porcine insulin when C peptide is measured; in either case allowing endogenous β-cell activity to be tested. Insulin (0.1 U/kg body weight) is given as a bolus intravenous injection. Other provocation tests, such as intravenous glucagon, tolbutamide, and oral leucine, are no longer used; the results are difficult to interpret and the procedures often produce dangerous hypoglycemia. Both hypergastrinemia and gastric acid hypersecretion are necessary for the diagnosis of gastrinoma in a patient presenting with recurrent peptic ulceration.