Impaired somatostatin response to orally administered glucose in type II diabetes entails both somatostatin-28 and -14 and is associated with deranged metabolic control.

UNLABELLED: We have investigated the effects of hyperglycemia in Type II diabetic patients on the somatostatin response to oral glucose. In these patients hyperglycemia prevailed (11.8 +/- 1.4 mmol/l) and was markedly increased to a maximum of 18.9 +/- 1.0 mmol/l following the ingestion of 75 g of glucose. The rise in blood glucose following glucose ingestion failed to induce a rise in plasma levels of somatostatin-like immunoreactivity. Biostator-regulated insulin infusion normalized fasting levels of blood glucose and reduced the hyperglycemia following glucose ingestion, i.e. blood glucose now rose from 4.6 +/- 0.1 to a maximum of 7.3 +/- 0.8 mmol/l. This moderate rise in blood glucose was accompanied by a significant (p less than 0.05) rise in somatostatin-like immunoreactivity. Somatostatin-28 and somatostatin-14 were separated using a Sephadex G-50 fine column. Biostator treatment suppressed plasma levels of both peptides during fasting conditions. Treatment was also accompanied by a rise in both peptides during the first hour following glucose ingestion; this rise did not occur in the untreated state. IN CONCLUSION: lack of somatostatin response to glucose in non-insulin-dependent diabetes mellitus is associated with deranged metabolic control. Unresponsiveness to glucose entails the secretion of both somatostatin-28 and -14.

Glucose and fructose 6-phosphate cycle in humans.

We have determined the rate of glucose cycling by comparing turnovers of [2-3H]- and [6-3H]glucose under basal conditions and during a glucose infusion. Moreover, the activity of the fructose 6-phosphate cycle was assessed by comparing [3-3H]- and [6-3H]glucose. The study included eight lean subjects with normal glucose tolerance. They participated in two randomly performed investigations. In one experiment [2-3H]- and [6-3H]glucose were given simultaneously, while in the other only [3-3H]glucose was given. The basal rate of glucose cycling was 0.32 +/- 0.08 mg X kg-1 X min-1 or 17% of basal glucose production (P less than 0.005). During glucose infusion the activity of endogenous glucose cycling did not change but since glucose production was suppressed it amounted to 130% of glucose production. The basal fructose 6-phosphate cycle could be detected only in three subjects and was suppressed during glucose infusion. In conclusion, the glucose cycle is active in healthy humans both in basal conditions and during moderate hyperglycemia. In some subjects, the fructose 6-phosphate cycle also appears to be active. Thus it is preferable to use [6-3H]glucose rather than [3-3H]glucose when measuring glucose production and particularly when assessing glucose cycle.

Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid.

A radioimmunoassay was developed for somatomedin-binding protein isolated from human amniotic fluid. The mean level in amniotic samples from 20-22 week of gestation was high, 51 micrograms/ml. Human serum and serum fraction gave dose-response curves superimposable on that for the pure amniotic binding protein. Gel chromatography of serum at neutral pH disclosed immunoreactive binding protein only in fractions with a molecular size of 35 000 corresponding to elution volume for the low molecular form somatomedin-binding protein. The mean levels (mean and range) of immunoreactive somatomedin-binding protein in cord blood (191 ng/ml, 55-1698 ng/ml) and in diabetic patients with uraemia (97 and 51-174 ng/ml) were 5- to 10-fold elevated above those of healthy adults (23 and 18-36 ng/ml). In acromegaly the levels decreased with increasing GH production (r = -0.77; P less than 0.005). In adult patients with GH deficiency the levels were 2-fold elevated in comparison with healthy subjects. Apart from patients with uraemia a negative correlation was found in adults between the levels of immunoreactive binding protein and immunoreactive IGF-I which reflect the GH production (r = -0.81, P less than 0.001).

A stimulating effect of glucose on somatostatin release is impaired in noninsulin-dependent diabetes mellitus.

The effect of oral glucose (1 g/kg BW) on levels of immunoreactive somatostatin (SLI) in peripheral venous plasma was investigated in young and older nondiabetic subjects (mean ages, 25.8 and 56.7 yr, respectively) as well as in subjects with decreased iv glucose tolerance (K value less than 1.0) and in diet-treated diabetic patients with fasting hyperglycemia (blood glucose, greater than 7.0 mmol/liter). SLI was assayed after extraction of plasma on silica glass beads. In control experiments (glucose omitted), SLI levels tended to decline. Ingestion of glucose was followed by a moderate (52% or less) increase in SLI levels in subjects with normal or decreased iv glucose tolerance. The stimulating effect was sustained for 90 or 120 min after glucose ingestion and the increase in plasma SLI was significant (P less than 0.05-0.02) whether in relation to prestimulatory values or control experiments. In contrast, in overtly diabetic patients, glucose ingestion was not followed by increased SLI levels. It is concluded that oral glucose stimulates SLI secretion in individuals of different ages and with varying degrees of glucose tolerance, but the response is impaired in type 2 diabetic patients with fasting hyperglycemia.

Insulin resistance and decreased insulin response to glucose in lean type 2 diabetics.

In an attempt to determine the mechanism of decreased glucose tolerance in lean type 2 diabetics, glucose turnover in such subjects and controls was studied under basal conditions and during hyperglycemia induced by intravenous administration of glucose. The diabetics had decreased intravenous glucose tolerance and a fasting plasma glucose of 6-8 mM (108-144 mg/dl). Glucose was infused for 2 hr at 2 mg/kg per min in the controls (n = 16) and diabetics (n = 9). Furthermore, 11 healthy subjects were infused also with glucose at 4 mg/kg per min to match the glycemia of the diabetics. Glucose production, utilization, and metabolic clearance were assessed by the primed constant tracer infusion technique. In the basal state, diabetics showed normal plasma insulin, C peptide, and glucagon concentrations. Their increased basal plasma glucose levels were associated with normal rates of glucose production and utilization, but the metabolic glucose clearance was 21% lower than in the controls (P < 0.001), indicating decreased sensitivity to insulin. During infusion of glucose at 2 mg/kg per min, the hyperglycemia attained in the diabetics (170 mg/dl) was higher than that in controls (115 mg/dl) but comparable to that of the controls exposed to the higher glucose load. With the lower glucose load, metabolic clearance rate decreased more markedly in diabetics, again suggesting insulin resistance. This was further substantiated by the fact that, at the same insulin levels, glucose utilization did not increase more in the diabetics than in the controls, although the glycemia reached was considerably higher in the diabetics. With the lower glucose load, glucose production was suppressed to the same degree in the controls and diabetics, although the attained glycemia was much more marked in the latter. Because both insulin and hyperglycemia can suppress glucose production, some defect in the regulation of glucose production of the diabetics is also indicated. The insulin and C peptide levels were much higher in the controls than in the diabetics at the same levels of glycemia, demonstrating the inadequacy of insulin response to glycemia of the diabetics. Glucagon concentration was equally suppressed in all groups. In conclusion, impaired glucose tolerance of mild type 2 diabetics resulted both from inadequate insulin response and from decreased sensitivity to insulin. The insulin resistance could mainly be ascribed to inadequate glucose uptake, but a defect in glucose-induced suppression of glucose production may also have contributed.

Decreased release of somatostatin into the portal vein following electrical vagal stimulation in the cat.

Electrical vagal stimulations were performed in anesthetized cats, in which the spleen and the intestine below the duodenum had been removed. The cats were provided with acute antral pouches which were perfused during the experiments. Insulin, glucagon, gastrin and somatostatin were measured in portal vein blood (consisting of blood from the stomach and the pancreas). The antral perfusates were analyzed for gastrin and somatostatin. Electrical vagal stimulation increased the release of insulin and glucagon into the portal vein. Gastrin was elevated in antral perfusates and portal vein blood, whereas somatostatin increased the antral perfusates, but was reduced in portal vein blood. We assume that antral somatotostatin, like gastrin, is released into the blood. The finding that portal vein somatostatin was decreased following vagal stimulation, indicates that the release of somatostatin from another large source of somatostatin, presumably the fundic region of the stomach or the pancreas, was decreased by vagal activation.