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SUMMARY

The influence of pancreatectomy on the blood sugar and on the serum lipids and ketone bodies has been examined in fifteen male baboons while receiving insulin as well as during periods of insulin deprivation. In insulin-treated baboons, a daily hyperglycaemia, alternating with periods of reduced blood-sugar concentration, was not associated with the development of a lipaemia. During insulin withdrawal, it was shown that (1) hyperlipaemia, cholesterolaemia, phospholipaemia and ketonaemia developed consistently in all baboons; (2) hyperglycaemia preceded lipaemia by 24–48 hr; (3) the triglycerides were the most sensitive fraction of the serum lipids, largely accounting for the initial lipaemia following insulin deprivation and showing the most rapid decline during the 24 hr following the re-administration of insulin; and (4) insulin exerted a transitory action on the blood sugar but a more prolonged one on the serum lipids. It is suggested that this differential action of insulin on the blood sugar and on the blood fats might assist in interpreting the seeming inconsistency between the severity of the diabetes and the observed levels of the blood fats in man.

No direct relationship could be established between the severity of the lipaemia or of the hyperglycaemia and the severity of the ketosis in insulin-deprived, depancreatized baboons. It is suggested that the wide variations in the levels of the serum lipids and of the ketone bodies following insulin withdrawal are indicative of subtle individual differences in the relative intensity of activity of the endocrine glands, particularly the adrenal cortex, the thyroid and the pituitary, in each baboon at any given moment.

SUMMARY

1. Xenopus laevis responds to injected adrenaline by an increase in the level of blood sugar. This increased blood sugar is apparently derived from liver and not from muscle glycogen.

2. Blood-sugar levels of Xenopus equilibrated on a black background (BB) and on a white background (WB) are statistically different throughout 6 months' starvation (P<0·05). On prolonged starvation for 14–16 months the lower blood-sugar level recorded in WB animals is not statistically different from that in BB animals (P> 0·10).

3. Xenopus shows a marked excitation hyperglycaemia, which is thought to be due to secretion of endogenous adrenaline. This hyperglycaemia is greatest in animals kept on a white background.

4. Xenopus equilibrated on black and white backgrounds show different hyperglycaemic responses to similar doses of adrenaline (P < 0·01). Compared with their own 'control-distilled water injection' levels, WB animals show an increase of blood sugar 40% higher than BB animals.

5. If melanophore-expanding hormone ('B') is an effective agent in decreasing the hyperglycaemic response to adrenaline, the greater effective level of circulating hormone in BB animals, together with their relatively reduced glycaemic response, supports the view that endogenous 'B' hormone plays a role in normal carbohydrate metabolism.

Hyperglycaemia was produced in chronically catheterized fetal lambs and pregnant ewes by the infusion of glucose into the fetus. Plasma concentrations of placental lactogen did not change significantly in either fetal or maternal circulations. Fetal and maternal hypoglycaemia was induced by administration of insulin to the fetus and ewe separately. Plasma concentrations of placental lactogen in the fetus did not change significantly but maternal plasma concentrations fell slightly after hypoglycaemia in either fetus or ewe. Plasma concentrations of placental lactogen rose in both the ewe and fetus during prolonged fasting of the ewe. These results neither confirm nor refute a role for placental lactogen in intermediary metabolism of the pregnant ewe and fetus but glucose concentration alone is unlikely to be a significant factor in the control of secretion of this hormone.

ABSTRACT

The effect of maternal hyperglycaemia on the function of neonatal B cells was examined using a perifusion technique in pancreatic monolayer cultures of neonatal rats from normoglycaemic mothers (C), and those made slightly hyperglycaemic (SH) and highly hyperglycaemic (HH) by injection of streptozotocin. Monolayer cultures were kept for 7 days in medium containing 5·5 mmol glucose/l plus 1 mmol 2-deoxy-glucose/l. On day 0, B cells in the C group responded to 16·7 mmol glucose/l, 10 mmol leucine/l and 10 mmol 2-ketoisocaproate/l in a monophasic fashion with no significant rise in the second phase. However, compared with the C group, a significant increase in the second-phase secretion in response to glucose and 2-ketoisocaproate was observed in the SH group, although there was no difference in the first-phase secretion. In the HH group the insulin secretion was lower in the first phase but not in the second phase. After culture for 7 days, B cells in the C group showed a biphasic response to the secretagogues, with a great increase in the second-phase secretion. In the SH group, the second phase of insulin secretion was increased but the increment was far less than that in the C group. The secretory response was remarkably low in the HH group compared with other groups. From these results, we conclude that at an early stage of culture slight maternal hyperglycaemia causes a hypersensitivity of neonatal B cells but impairs the normal development of the function of B cells during culture, and that high hyperglycaemia results in impaired insulin secretion throughout the whole period of culture studied.

J. Endocr. (1988) 119, 493–499

SUMMARY

1. Estimations of monoamine oxidase (m.o.) activity in suspensions of frog liver taken at monthly intervals showed that activity was relatively constant during the greater part of the year (mean value 8·6 ± 0·332 μl. O₂/15 min/mg colloid nitrogen), but it rose to a significantly higher level from August to November inclusive (mean 11·7 ± 0·513 μl. O₂/15 min/mg colloid nitrogen).

2. The pattern of seasonal variation in enzyme activity showed no correspondence with the annual cycle of change in the thyroid gland, nor was there any correlation between m.o. activity of the liver and the histological appearance of the thyroid in individual frogs.

3. Inhibition of m.o. in vivo by iproniazid elicited a hyperglycaemic response to excitement in previously unresponsive frogs which was almost identical with that obtained after treatment with thyroxine and iproniazid.

4. There was no evidence that treatment with thyroxine led to any alteration in the activity of liver m.o.

5. It is concluded that m.o. is not an important factor in the inactivation of catechol amines in the strongly stimulated frog, but the possibility is discussed that under natural conditions of lower stress the high enzyme activity from August to November might be one factor tending to limit mobilization of liver glycogen.

SUMMARY

The mean blood-sugar level of frogs killed in the field without previous excitement showed no significant variation between April and October inclusive (38±1·42 mg/100 ml.). The resting blood-sugar level at other times of the year, after 2–3 days in captivity, was slightly lower.

A marked hyperglycaemic response to excitement could be elicited in the majority of frogs at the spawning season (March) and throughout the summer, while it was only found in April and early May in a few frogs which showed early development of the gonadial fat-bodies. The response was much reduced in September and absent in October.

The seasonal occurrence of the hyperglycaemic response paralleled the known cycle of thyroid activity, and a significant correlation was found between the blood-sugar level and thyroid condition in individual excited frogs. A significant response to excitement has been induced in spring, summer and autumn by previous treatment with thyroxine. It is suggested that the thyroid hormone inhibits the destruction of circulating adrenergic compounds.

The role of temperature in limiting the hyperglycaemic response is discussed.

ABSTRACT

Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet β-cells from these two mouse strains, with different sensitivities of their β-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5·6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5·6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1·7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l. Insulin mRNA content was increased in islets cultured in 28 or 56 mmol glucose/l from both mouse strains. Glucose metabolism showed no differences in the rates of glucose oxidation, however, in islets cultured in 56 mmol glucose/l the utilization of glucose was increased in both BL/6J and BL/KsJ animals. There were no differences in DNA content in islets cultured at different glucose concentrations, suggesting no enhancement of cell death.

The present study indicates that, irrespective of genetic background, murine β-cells can adapt to very high glucose concentrations in vitro without any obvious signs of so-called glucotoxicity. Previously observed signs of glucotoxicity in vivo in BL/KsJ islets appear not to be related only to glucose but rather to an additional factor in the diabetic environment.

Journal of Endocrinology (1993) 136, 289–296