Biomedical subjects

P C Mathias

Publications and source records attributed to P C Mathias.

24 records · Page 2Linked to original sources

PubMed1984

Methylamines and islet function: cationic aspects.

Methylamine (2 to 10 mM) caused a dose-related inhibition of insulin release evoked in rat pancreatic islets by nutrient or non nutrient secretagogues. Trimethylamine exerted comparable effects upon insulin release. Methylamine (2 mM) inhibited insulin secretion but failed to affect 45Ca uptake and efflux in response to a rise in extracellular K+ concentration, suggesting that methylamine acts, to a certain extent at least, at a distal site in the secretory sequence. Methylamine, however, also exerted untoward ionic effects. First, methylamine (2 to 10 mM) apparently caused a dose-related increase in cellular pH. Second, methylamine (2mM) augmented 86Rb outflow from islets perifused either in the absence or presence of glucose or gliclazide, and inhibited Ca2+ inflow (as judged from the net uptake or efflux of 45Ca) in islets stimulated by D-glucose, L-leucine or 2-ketoisocaproate. This multiplicity of ionic and other effects may account for the fact that, in the presence of distinct secretagogues, the secretory process appeared more or less sensitive towards methylamine, depending on the relative importance of changes in cellular pH, K+ permeability and intracellular Ca2+ distribution as determinants of the secretory response.

Acyltransferases↗

PubMed1984

Inhibition by corticosterone of calcium inflow and insulin release in rat pancreatic islets.

Corticosterone (0.6 mumol/l) inhibited both 45Ca outflow and insulin release evoked by glucose, the combination of leucine and glutamine, 2-ketoisocaproate, gliclazide or the association of gliclazide and a tumour-promoting phorbol ester in rat pancreatic islets perifused at normal extracellular Ca2+ concentration (1.0 mmol/l). In all cases, the inhibitory action of corticosterone reached statistical significance within 10-22 min of exposure to this steroid and failed to be rapidly reversible. Corticosterone failed to affect basal 45Ca outflow and insulin release. The steroid also failed to affect the inhibitory action of glucose upon 45Ca outflow, as judged from either the glucose-induced early fall in effluent radioactivity from islets maintained at normal extracellular Ca2+ concentration or the steady-state values for 45Ca outflow from glucose-stimulated but Ca2+-deprived islets. Corticosterone caused a modest increase in 86Rb outflow from islets perifused in the presence of glucose (16.7 mmol/l). It is concluded that corticosterone impairs Ca2+ inflow into the islet cells and, by doing so, causes a progressive inhibition of insulin release. The pancreatic B cell might thus serve as a further model for the study of the rapid biological response to steroids, as presumably mediated by alteration in the biophysical properties of the plasma membrane.

Animals↗

PubMed1984

Inhibition of transglutaminase by hypoglycaemic sulphonylureas in pancreatic islets and its possible relevance to insulin release.

Pancreatic islet homogenates display calcium-sensitive transglutaminase activity, but the role of this enzyme in the process of insulin release remains to be elucidated. Tolbutamide, gliclazide, glisoxepide, glipizide and glibenclamide inhibited transglutaminase activity in islet homogenates. When the cationic response of islet cells to hypoglycaemic sulphonylureas was suppressed by exposing intact islets to quinine, tolbutamide, gliclazide and glibenclamide caused a rapid, sustained, reversible and dose-related inhibition of insulin release. The relative efficiency of distinct hypoglycaemic sulphonylureas as inhibitor of transglutaminase activity was in mirror image of their relative potency as insulin secretagogue. However, the dose-action relationship for the inhibitory action of these agents upon insulin release from quinine-treated islets was similar in response to either tolbutamide, gliclazide or glibenclamide. These results indicate that hypoglycaemic sulphonylureas may exert an inhibitory action upon insulin release, but suggest that such an effect is not tightly related to inhibition of transglutaminase.

Acyltransferases↗

PubMed1984

Influence of extracellular pH upon the ionic and secretory response to gliclazide in pancreatic islets.

The influence of extracellular pH upon the ionic and secretory response to gliclazide was examined in perifused rat islets. Gliclazide usually decreased 86Rb outflow from the islets except in the presence of glucose (7.0 mM) and Ca2+ (1.0 mM) and at low (7.0) or normal (7.4) pH, in which cases it caused a rapid increase in 86Rb output. Gliclazide failed to affect 45Ca outflow in the absence of extracellular Ca2+, whatever the extracellular pH. However, in the presence of Ca2+ and glucose (7.0 mM), gliclazide enhanced 45Ca outflow and insulin release. Under the latter experimental conditions, the gliclazide-induced increment in both 45Ca and insulin output was progressively increased as the pH was raised from 7.0 to 7.4 and 7.8, despite the fact that glucose-induced insulin release was progressively decreased over the same pH range. The gliclazide-induced facilitation of Ca2+ inflow into the islet cells and the subsequent stimulation of insulin release, whatever their precise molecular determinants, thus displayed the same dependency towards extracellular pH as that characterizing the ionophoretic action of the drug. The influence of extracellular pH upon the cationic and secretory response to gliclazide is compatible, therefore, with the view that the insulinotropic action of hypoglycemic sulfonylureas is somehow related to their ionophoretic capacity.

Animals↗

PubMed1983

Comparison of the cationic and secretory response of pancreatic islets to gliclazide and/or potassium.

The concept that hypoglycemic sulfonylureas stimulate Ca2+ inflow and insulin release in the pancreatic B-cell by causing the gating of voltage-sensitive Ca2+ channels was tested by comparing the cationic and secretory response of perifused pancreatic islets to gliclazide and/or an increase in extracellular K+ concentration. In the presence of glucose (2.8 mM), both procedures resulted in an immediate and sustained stimulation of 45Ca and insulin release from prelabelled islets. The capacity of gliclazide to stimulate 45Ca and insulin release persisted, to a limited extent, in islets exposed to 20 mM K+, but was abolished in islets exposed to 50 mM K+. At the latter concentration, however, K+ was still able to augment 45Ca outflow and insulin secretion from islets first exposed to gliclazide. These findings support the view that the depolarization of the B-cell membrane plays a critical role in the stimulus-secretion coupling of sulfonylurea-induced insulin release.

Animals↗

PubMedDate not supplied

Vagotomy reduces obesity in MSG-treated rats.

In order to study the role of vagus nerve activity at the onset of obesity induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or sham operated. Body weight and food intake were recorded until animals were 90 days old and then sacrificed. Naso-anal length was recorded for all animals. Periepididymal and retroperitoneal fat pads were isolated and weighed. Reduction of body weight and naso-anal length were registered in 30-day-old MSG-rats. Obesity could also be observed, as increase of Lee index indicated. Results were most evident in 90-day-old MSG-rats. In both groups neither body weight gain nor food intake was changed by vagotomy. However, fat accumulation on tissues was reduced by vagotomy in MSG-rats. The results showed that MSG-obesity is not related to an increment in food intake behavior. Vagotonia might play a role at the onset of MSG-obesity.

Animals↗