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ABSTRACT

Experiments were carried out on Sprague–Dawley rats to determine whether changes in fetal corticosterone levels during maternal diabetes were caused by the accompanying fetal hyperinsulinaemia or fetal hyperglycaemia. Diabetes was induced by injecting streptozotocin (30–45 mg/kg, i.v.) on day 2 of gestation. Fetal adrenals were removed on day 20 of gestation and cultured. Streptozotocin caused moderate (blood glucose 14–22·5 mmol/l) to severe (blood glucose >25 mmol/l) diabetes. Both moderate and severe diabetes caused a decrease in fetal body weights. Relative to non-diabetic controls, maternal and fetal plasma concentrations of corticosterone were higher in the severely and lower in the moderately diabetic rats. Corticosterone production by fetal adrenal cells from control and moderately diabetic rats was comparable, but cells from the severely diabetic animals produced significantly greater amounts of corticosterone than did control cells. Neither glucose (28 mmol/l) nor insulin (1 nmol/l) exerted significant effects on [³H]thymidine uptake or corticosterone production by fetal adrenal cells from non-diabetic, moderately diabetic or severely diabetic rats. Human ACTH (0·02–20 nmol/l) caused a concentration-dependent increase in corticosterone output of comparable magnitude by cells from all three groups of animals. These data suggest that fetal growth abnormalities during diabetic pregnancy are not directly related to changes in glucocorticoid levels and that changes in glucocorticoid levels are not caused by any direct action of fetal hyperinsulinaemia or hyperglycaemia on adrenal cells.

Journal of Endocrinology (1989) 120, 393–399

Bilateral hind-limb ischaemia in the rat is known to cause insulin resistance, as shown by a sustained rise in plasma glucose concentration with a decreased metabolic clearance rate but no fall in plasma insulin. However, when the concomitant rise in the plasma concentration of corticosterone was diminished by an inhibitor of its biosynthesis, trilostane (WIN 24 540), the hyperglycaemia became transient. The mechanism of this effect has now been studied by measuring the rate of disappearance of [5-³H,U-¹⁴C]glucose and the concentration of insulin in plasma. Trilostane did not alter the rate of glucose production or the ³H: ¹⁴C ratio (an index of recycling through gluconeogenic precursors). It did, however, raise the metabolic clearance rate while lowering the plasma insulin concentration, i.e. peripheral sensitivity and/or responsiveness to insulin was increased. Insulin resistance was restored by giving corticosterone together with trilostane. Thus an increased concentration of corticosterone in the plasma was necessary for the full development of insulin resistance following ischaemic limb injury. It was, however, probably not the only factor since a similar dose of corticosterone did not lead to hyperglycaemia in uninjured rats.

SUMMARY

The i.v. injection of 50 μg/kg body weight of adrenaline hydrochloride prior to the injection of diabetogenic doses of alloxan has a protective effect in the dog.

This protection has a duration exceeding that of the vasoconstrictor action of adrenaline.

It is concluded that the protective effect may depend initially on alterations in the circulation of the pancreas brought about by adrenaline and may afterwards be maintained by the postadrenaline hyperglycaemia.

The administration of 2 i.u./kg body weight of insulin by i.m. injection 2 hr before the injection of adrenaline diminishes or abolishes the protection phenomenon.

This interference of insulin with the protective effect of adrenaline depends upon the hypoglycaemia which sensitizes the β-cells of the pancreas to alloxan.

The i.v. injection of 2 i.u./kg body weight of insulin 5 min before the injection of adrenaline does not prevent its protective effect.

ABSTRACT

Amylin-amide has been implicated in the pathogenesis of type II diabetes due to its proposed inhibitory effect on insulin release from β cells of the pancreatic islets, and on glucose uptake by the skeletal muscle. In experiments with rats and rabbits we failed to demonstrate these anti-insulin actions of amylin and amylin-amide. A single bolus dose of the two peptides (500 pmol) administered i.v. failed to supress plasma insulin levels or to elevate blood glucose levels. The continuous infusion of amylin-amide into rabbits also failed to supress the release of insulin in response to hyperglycaemia produced by an i.v. bolus injection of glucose. These in vivo observations imply that the amylin peptides may not have a primary physiological role in carbohydrate metabolism, but in view of our previous findings, we speculate that the peptide has a more prominent role in calcium homeostasis.

ABSTRACT

The relationships between plasma concentrations of energy substrates and placental lactogen (PL) were investigated in pregnant ewes. In successive hourly samples of plasma PL, concentrations varied by ± 30% but were not related to general activity or feeding of the ewes or the time of day. Fasting ewes for 72 h did not alter the pattern or the mean PL titres. Insulin-induced acute hypoglycaemia, hyperglycaemia and decreases or increases in free fatty acids (FFA) all failed to alter PL levels significantly during 5-h post-treatment periods. These experiments demonstrate that PL secretion in the ewe fluctuates markedly and is unaffected by changes in plasma glucose or FFA concentrations.

J. Endocr. (1987) 114, 391–397

ABSTRACT

The mechanism responsible for the suppression of GH secretion in hyperglycaemia and hypoglyceamia in rats has been investigated using perifusion of anterior pituitary cells. When perifused with Krebs-Ringer bicarbonate containing normal (5 mmol/l), high (20 mmol/l) and low (1 mmol/l) concentrations of glucose, the GH responses to GH-releasing factor (GRF) were 85 ± 5, 85·5 ± 5·4 and 89 ± 3·0 (s.e.m.)% respectively compared with the initial response to GRF at 5 mmol/l in each column. The mean GH response to GRF from anterior pituitary cells of normal rats was 6·58 ± 0·88 μg/three pituitaries, which was not statistically different from that of cells from rats with streptozotocin-induced diabetes (5·40 ± 0·68 μg/three pituitaries). It is concluded that GH suppression in diabetic rats and during hypoglycaemia is not mediated by changes in the GH response to GRF.

Journal of Endocrinology (1989) 122, 657–660

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.

The effects of adrenaline and amino acids on β-cell function have been investigated in chronically catheterized fetal sheep. Infusion of adrenaline (1 μg/min) abolished the normal β-cell response to both glucose and arginine. The adrenaline infusion also caused hyperglycaemia and a reduction in the basal plasma insulin concentration in the fetus in the period before the infusion of glucose or arginine was given. Infusion of amino acids increased the speed and the magnitude of the β-cell response to glucose. The maximum increment in the fetal insulin level in response to glucose was 68·5 ± 13·5 (s.e.m.) μu./ml (n = 5) during amino acid infusion which was significantly greater than the value of 16·1 ± 3·4 μu./ml observed in the control experiments. The observations are discussed in relation to the regulation of insulin release in utero.

SUMMARY

The effect of glucose on the release of insulin from the pancreas of 18·5 to 21·5-day-old rat foetuses has been studied in utero. Foetal hyperglycaemia was induced by a 1 h glucose infusion into pregnant rats.

In foetuses from mother rats infused with saline, the blood glucose and the plasma insulin concentrations increased up to day 21·5 of gestation. The blood glucose level of the foetuses never exceeded that of the mothers which remained stable from day 18·5 to day 21·5 of gestation.

The infusion of glucose raised the foetal blood glucose concentration to that of the mothers and induced a significant increase of plasma insulin levels both in the mothers and their foetuses. The enhanced plasma insulin concentration observed in the 18·5-day-old foetuses of glucose-infused pregnant rats became greater each day up to 21·5 days.