Glucose-dependent insulin-releasing peptide in noninsulin-dependent maturity-onset diabetes: effects of autonomic neuropathy.

Glucose-dependent insulin-releasing peptide or gastric inhibitory polypeptide (GIP) is released into the circulation after ingestion of a mixed meal and is thought to enhance glucose-induced insulin release. We investigated basal and meal-stimulated GIP secretion in noninsulin-dependent maturity-onset diabetics (MODs). Twelve MODs and 12 healthy normal subjects were studied. Mean (+/- SE) basal plasma GIP concentrations were similar in MODs (297 +/- 34.5 pg/ml) and healthy subjects (305 +/- 29.7 pg/ml). Overnight insulin infusion normalized basal glucose levels in the MODs and induced a slight but insignificant rise in plasma GIP levels in MODs to 362 +/- 40.9 pg/ml; overnight gastric aspiration caused a further slight rise in basal GIP concentration to 392 +/- 56.6 pg/ml. The GIP responses to a mixed meal were significantly impaired at 90-240 min in MODs. The MODs were divided into 2 groups, each with 6 subjects: 1 group with autonomic neuropathy (AN) and the other without. The GIP responses in MODs without AN were similar to those in healthy subjects, but were significantly reduced in MODs with AN at all times after the meal. We suggest that the release of GIP after a meal is dependent upon the integrity of the autonomic nervous system; the mechanism may be related to the loss of autonomic control of gastric emptying or dependence of GIP secretion on autonomic modulation.

The effect of dietary fiber on glucose and hormone responses to a mixed meal in normal subjects and in diabetic subjects with and without autonomic neuropathy.

We investigated the effects of fiber on responses of blood glucose, serum insulin, gastric inhibitory polypeptide (GIP), and immunoreactive pancreatic glucagon (IRG) to ingestion of mixed meal with and without added fiber (5 g guar and 5 g pectin) in 12 normal, healthy subjects and in 12 age-, sex-, and weight-matched non-insulin-dependent, maturity-onset diabetic subjects (NIDDM). Fiber markedly enhanced glucose tolerance in the normal subjects without a change in insulin or GIP but with a significant reduction in glucagon responses. Fiber also markedly improved glucose tolerance in the NIDDMs without changing insulin or GIP but with a significant reduction in the glucagon responses. The NIDDMs were divided into two groups of six subjects, with and without autonomic neuropathy (AN). In NIDDMs without AN, glucose tolerance was improved by fiber without a change in insulin, IRG, or GIP. In diabetic subjects with AN, glucose tolerance was not improved, although glucagon levels were lowered and insulin and GIP responses were unchanged. It appears, therefore, that fiber improves glucose tolerance by altering factors other than insulin. It seems also that autonomic nervous supply to the gastrointestinal tract is important in mediating the effect.

Gastric inhibitory polypeptide in acquired pancreatic diabetes: effects of insulin treatment.

Oral glucose tolerance tests were done in eight insulin-requiring pancreatic diabetic patients to study the effect of withdrawal of insulin treatment on gut hormone release. Basal levels of gastric inhibitory polypeptide (GIP), glucagon-like immunoreactivity, and immunoreactive glucagon levels rose on insulin withdrawal, more so in patients on short-acting insulin, and were lowered by insulin treatment. Insulin treatment did not affect the GIP, glucagon-like immunoreactivity, or IRG responses to oral glucose. Improved glucose tolerance was greater in patients receiving soluble insulin than in those receiving lente insulin, and there was a significant positive linear correlation between basal plasma GIP and blood glucose levels in these patients. Therefore, it is suggested that insulin treatment lowers basal hormones levels, possibly via a metabolic effect, whereas the hormone responses to oral glucose may be controlled by several factors unrelated to insulin administration or changes in glucose homeostasis.

Inhibition of exaggerated gastrointestinal glucagon responses in chronic pancreatitis by somatostatin.

Oral glucose administration caused an exaggerated release of cross-reacting gastrointestinal glucagon-like immunoreactivity (GLI) and a slight early rise in immunoreactive glucagon (IRG) concentration in patients with chronic pancreatitis, who have impaired insulin release. Intravenous administration of 200 microgram of somatostatin, followed by infusion of 200 microgram over 2 1/2 h, abolished the GLI and insulin responses, but did not change glucose tolerance. This contrasts with the relatively minor effects of somatostatin on GLI responses in control subjects where the clear deterioration in glucose tolerance may relate to inhibition of insulin release.

The effects of somatostatin on hormonal and metabolic responses in chronic pancreatitis.

Unmodified synthetic somatostatin, given as a 200-microgram intravenous bolus, plus 200 microgram infused over 3 hours, had no effect on basal plasma insulin and pancreatic glucagon-like immunoreactivity (GLI) levels, both in controls and in patients with chronic pancreatitis. Somatostatin inhibited insulin-hypoglycaemia-induced pancreatic GLI release in controls and in patients with pancreatitis, and prolonged the insulin-induced fall in blood glucose in the patients. Arginine, presumably via insulin release, caused a fall in free fatty acids (FFA) in controls, which was inhibited by somatostatin. Somatostatin abolished the rebound rise in plasma FFA in patients with pancreatitis after insulin-hypoglycaemia. This effect may be related to inhibition of pancreatic GLI release or may be a direct action of somatostatin on lipolysis.

Pancreatic glucagon-like immunoreactivity in a pancreatectomized patient.

True or 'pancreatic' glucagon-like immunoreactivity (GLI) was found in the plasma of a pancreatectomized patient. In contrast with the regulation of pancreatic GLI in normal controls, there was paradoxical release after oral glucose, no response to arginine or insulin-hypoglycaemia and somatostatin did not suppress its release, but tolbutamide did. Similar to controls, this pancreatic GLI appeared to be under adrenergic beta-receptor control. There was no apparent effect on blood glucose regulation despite marked changes in pancreatic GLI levels during the various manipulations. On polyacrylamide gel electrophoresis, pancreatic GLI from our patient's plasma eluted as two equivalent peaks: one with the glucagon marker and the other in a more cathodal position. We therefore suggest that, although the extra-pancreatic 'pancreatic' GLI in our patient's plasma has immunologic similarities with pancreatic glucagon, the responses to stimulation and suppression are quite different from those in controls and the biologic activity does not appear to be that of pancreatic glucagon.