Biomedical subjects

J C Hutton

Publications and source records attributed to J C Hutton.

138 records · Page 8Linked to original sources

PubMed1978

The stimulus secretion coupling of glucose-induced insulin release. XXVII. Effect of glucose on K+ fluxes in isolated islets.

The effect of glucose upon the handling of K+ by islets of Langerhans removed from normal rats was investigated by measuring both the net uptake of 86Rb+ and its efflux from prelabelled islets. The inflow of K+ into islet cells is mediated, in part at least, by an ouabain-sensitive pump. Glucose fails to affect the inflow rate of K+, but it apparently decreases the permeability of islet cells plasma membrane to effuent K+. The glucose-induced change in permeability is a rapid and rapidly reversible phenomenon. Under steady-state conditions, it leads to an increase in the islet cells K+ pool and a decrease of its fractional turnover rate.

Animals↗

PubMed1978

Calcium antagonists and islet function: VII. Effect of calcium deprivation.

The role of extracellular Ca2+ in the regulation of islet function is investigated. Decreasing extracellular Ca2+ concentrations cause a dose-related inhibition of glucose-induced insulin release. Whereas the efflux of 45Ca from perifused islets is transiently increased on exposure to Ca2+-deprived media, it is unaffected by a partial lowering of the extracellular Ca2+ concentration. Under the latter condition, therefore, the observed reduction in the size of the islets' exchangeable calcium pool(s) appears to be due to reduced Ca2+ entry. The proper effect of glucose on Ca handling by the islets is apparently not affected by a lowering in the extracellular Ca2+ concentration. Nevertheless, in islets exposed to glucose and incubated in Ca2+-deprived media, glucose uptake and oxidation and lactate output are decreased, whereas the islet ATP level is increased, as if extracellular Ca2+ shortage were to affect not only the cellular pool of Ca regulating insulin release, but also energy-consuming processes possibly located at the cell membrane.

Adenosine Triphosphate↗

PubMed1978

The stimulus-secretion coupling of glucose-induced insulin release. Metabolic and functional effects of NH4+ in rat islets.

NH4+ caused a dose-related, rapid, and reversible inhibition of glucose-stimulated insulin release by isolated rat islets. It also inhibited glyceraldehyde-, Ba2+-, and sulfonylurea-stimulated insulun secretion. NH4+ failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, AD, and AMP, and the intracellular pH. NH4+ also failed to affect the ability of theophylline and cytochalasin B to augment glucose-induced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration of NADH and HADPH and a concomitant alteration of 86Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous of exogenous nutrients, may modulate ionophoretic processes in the islet cells and by doing so, affect the net uptake of Ca2+ and subsequent release of insulin.

Ammonia↗

PubMed1976

The effect of an unsaturated-fat diet on cataract formation in streptozotocin-induced diabetic rats.

1. Cataract formation in streptozotocin-induced diabetes in rats was reduced by approximately 85% when a diet rich in maize oil (300 g/kg diet) (fat diet) was given, thus confirming results of earlier studies. However, the concentration of sorbitol in the lens of diabetic animals remained high, the values for diabetic rats given the standard diet and the fat died being 65 and 40 mumol/g protein respectively. 2. With the standard diet, the fatty acid profile of the triglycerides of the epididymal fat pads was characterized by a greater relative proportion of saturated fatty acids for the diabetic animals compared to that for the normal animals. The fat diet moderated the tendency towards saturation in the diabetic animals. 3. The fat diet had other effects on the diabetic animals; these included a reduced mortality rate, increased body-weight, a decrease in the daily water intake, and in the daily urinary excretion of glucose and urea. 4. In the diabetic animals the fat diet had no effect on the specific activities in the liver of hexokinase (EC 2.7.1.1), glucokinase (EC 2.7.1.2), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40). However, the specific activity of glucose-6-phosphatase (EC 3.1.3.9) was reduced, while that of malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was increased. The NAD+:NADH ratio, as calculated from liver pyruvate and lactate concentrations, tended to increase. 5. The results suggested that the fat diet moderated the long-term metabolic effects of diabetes.

Animals↗

PubMed1975

The localisation of sorbitol pathway activity in the rat renal cortex and its relationship to the pathogenesis of the renal complications of diabetes mellitus.

A series of in vivo and in vitro investigations was performed to examine the localisation of sorbitol pathway activity in the rat renal cortex and to investigate the possible relation that the acculumation of sorbitol pathway intermediates in renal cortical tissue may have to the pathogenesis of renal complications in diabetes mellitus. Neither of the sorbitol pathway intermediates, sorbitol or fructose, were detected either in intact glomeruli which had been isolated from rats rendered chronically diabetic with streptozotocin, or in metabolically active glomeruli which had been incubated in vitro in high glucose media. Such data agreed with previously published observations that the enzyme aldose reductase is not present in renal glomeruli, and suggested that changes in sorbitol pathway activity cannot be directly related to the pathogenesis of diabetic glomerulosclerosis. Sorbitol was detected in low concentrations (3.1 mu-mol/g protein) in cortical tubules which had been isolated from the renal cortex of rats rendered chronically diabetic with streptozotocin. This concentration of sorbitol was higher than that in the intact renal cortex of the diabetic animal (0.3 mu-mol/g protein) or in the cortical tubules of non-diabetic animals (0.5 mu-mol/g protein). It is apparent that the renal cortical tubule is a major site of sorbitol pathway activity in the renal cortex. However, there is presently no obvious causal relationship between the accumulation of such relatively low concentrations of sorbitol in the renal cortical tubule and the pathogenesis of glomerulosclerosis or cortical tubular lesions in diabetes.

Animals↗

PubMed1975

Osmotic effects of sorbitol accumulation in monkey kidney epithelial cell cultures.

It has been observed that primary monolayer cell cultures derived from monkey kidney cortex behave in a similar manner to the mammalian lens in that they accumulate high concentrations of sorbitol when they are incubated in medium containing a high glucose concentration (33 mM). An investigation was undertaken to determine whether the accumulation of sorbitol by these cultures results in cellular damage by an osmotic mechanism similar to that which has been proposed to occur in the lens. Phase-contrast microscopy and histochemical investigations revealed that no changes in the cell size, cell growth rate, or cell staining properties occurred as a result of exposure of the cell cultures to a glucose concentration of 33mM for up to 4 days. The cell protein and myo-inositol concentrations and fatty acid composition were also unaffected, as was the incorporation of radioactivity from [U-14C]leucine into cell protein. The rate of 86Rb influx of the cell cultures was decreased and the rate of 86Rb efflux was increased by incubation in medium containing a glucose concentration of 33 mM. Frome these observations it was concluded that the accumulation of sorbitol by monkey kidney epithelial cell cultures did not exert a pathabolic influence upon their growth and metabolism, and that these cells, unlike the lens, have the capacity to compensate adequately for changes in transmembrane osmotic gradients induced by sorbitol accumulation.

Animals↗

PubMed1974