Biomedical subjects

B Billaudel

Publications and source records attributed to B Billaudel.

At least 19 recordsLinked to original sources

PubMed2006

Effect of GSM-900 and -1800 signals on the skin of hairless rats. I: 2-hour acute exposures.

PURPOSE: The acute influence on the skin of non-ionizing electromagnetic fields in the radiofrequency (RF) range used in mobile telephony has not been widely studied to date. The purpose of this work was to determine whether the cells of hairless rat skin are affected by acute local exposure to Global System for Mobile Communication: GSM-900 or -1800 RadioFrequency Radiation (RFR). MATERIALS AND METHODS: Hairless female rats were exposed or sham-exposed for 2 h to GSM-900 or -1800 signals, using a loop-antenna located on the right part of the rats' back. The local Specific Absorption rate (SAR) at skin level was ca. 5 W/kg (5.8+/-0.4 and 4.8+/-0.4 W/kg at 900 and 1800 MHz, respectively). A skin biopsy was done at the end of the experiment not only at the location of exposure, but also on the symmetrical part of the back. RESULTS: Analysis of skin sections using Hematoxylin Eosin Saffron (HES) coloration showed no difference in skin thickness or apparent cell toxicity (with no sign of cellular necrosis) among the animal groups. Histological analysis of the epidermis showed that the ratio between cells expressing the antigen Ki-67 (cellular proliferation marker) and the total number of cells remained within the range of normal proliferation ratio for the exposed side of the animal. No Ki-67 labelling was observed at the dermis level. Results on filaggrin, collagen and elastin levels also showed an insignificant influence of RFR. CONCLUSIONS: These results do not demonstrate any major physical and histological variations at skin level induced by RFR used in mobile telephony.

Animals↗

PubMed2006

Effect of GSM-900 and -1800 signals on the skin of hairless rats. II: 12-week chronic exposures.

PURPOSE: The purpose of this work was to determine whether the cellular components of Hairless-rat skin are affected by a chronic local exposure to non-ionizing radiations of Global Mobile Phone System: GSM-900 or -1800 radiations at specific absorption rate (SAR) 2.5 and 5 W/kg. MATERIALS AND METHODS: A selected part of the right back of five-week old female hairless rats was exposed or sham exposed (n = 8) for 2 h per day, 5 days a week, for 12 weeks to GSM-900 or -1800 signals using a loop-antenna. At the end of the experiment, skin biopsies were taken. RESULTS: Analyses of skin sections using hematoxylin eosin saffron (HES) coloration showed no significant difference in skin thickness among the groups. Immunohistochemical analysis of basal lamella cells in radiofrequency radiation (RFR)-exposed epidermis showed that the ratio of the antigen Ki-67 (cellular proliferation marker) positive cells to total lamella cells remained within the range of the normal proliferation ratio. No significant differences in the level of filaggrin, collagen, and elastin were observed among the different groups. CONCLUSIONS: The results of this 12-week chronic study do not demonstrate major histological variations in the skin of hairless rats exposed to RFR used in mobile telephony (GSM-900 or -1800).

Animals↗

PubMed2003

Effects of GSM-900 microwaves on the experimental allergic encephalomyelitis (EAE) rat model of multiple sclerosis.

The effects of acute exposure to GSM-900 microwaves (900 MHz, 217 Hz pulse modulation) on the clinical parameters of the acute experimental allergic encephalomyelitis (EAE) model in rats were investigated in two independent experiments: rats were either habituated or nonhabituated to the exposure restrainers. EAE was induced with a mixture of myelin basic protein and Mycobacterium tuberculosis. Female Lewis rats were divided into cage control, sham exposed, and two groups exposed either at 1.5 or 6.0 W/kg local specific absorption rate (SAR averaged over the brain) using a loop antenna placed over their heads. There was no effect of a 21 day exposure (2 h/day) on the onset, duration, and termination of the EAE crisis.

Animals↗

PubMed2003

Effects of ELF and static magnetic fields on calcium oscillations in islets of Langerhans.

Several experimental studies have produced contradictory results on the effects of extremely low frequency (ELF) magnetic fields on cellular processes involving calcium ions. Furthermore, the few positive results have not been independently replicated. In most of these studies, isolated cells were used. Our study used mouse islets of Langerhans, in which very regular oscillations of calcium concentration can be observed at length. These oscillations are sustained by processes that imply energetic and inter-intracellular communication. Various magnetic fields were applied, either sinusoidal at different frequencies (50 Hz or multiples of the natural oscillation frequency) at 0.1 or 1 mT or static at 1 mT. Islets were also exposed to "cyclotron resonance" conditions. There was neither alteration of the fundamental oscillation frequency nor the degree of organisation under all exposure conditions. Using this sensitive model, we could not show new evidence of alterations of calcium processes under exposure to various magnetic fields.

Animals↗

PubMed1999

Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas.

Because 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is known to activate the biosynthesis of numerous proteins in various tissues, experiments were undertaken to compare the influence of 1,25(OH)2D3 in vitro on both the secretion and biosynthesis of insulin in islets of Langerhans from both 4-week vitamin D3-deficient rats and normal rats. Islets were either incubated or perifused after a 6-h induction period in the presence of various concentrations of 1, 25(OH)2D3 from 10(-12) M, which was inactive in controls, to 10(-6) M. Experiments were performed in the presence of a non-labelled amino acid mixture, to favour protein synthesis. Tritiated tyrosine was added as tracer during glucose stimulation. The newly synthesised proteins, labelled with [3H]tyrosine, were extracted by an acid-alcohol method and separated by gel chromatography adapted for low-molecular-weight proteins. Even in the presence of the amino acid mixture, the insulin response of the islets to 16.7 mM glucose was decreased by vitamin D3 deficiency and improved by 1,25(OH)2D3. This beneficial effect did not occur in basal conditions, but only during glucose stimulation, and was observed in both phases of insulin release. Moreover, these effects disappeared in the presence of 5x10(-4 )M cycloheximide, a protein biosynthesis inhibitor. Islets from vitamin D3-deficient rats exhibited a general decrease in the amount of de novo biosynthesised proteins and of [3H]tyrosine-labelled insulin and proinsulin fractions. A 6-h period of 1,25(OH)2D3 induction significantly improved the amount of de novo biosynthesised proteins, and particularly of newly synthesised insulin in response to a 2-h glucose stimulation. Calculation of the rate of conversion of newly synthesised proinsulin-like material to insulin as the [3H]insulin/[3H]proinsulin-like material ratio provided evidence for a dose-dependent increase, induced by 1, 25(OH)2D3, that could exceed that of normal islets. These data support the hypothesis that 1,25(OH)2D3 in vitro not only facilitated the biosynthetic capacity of the beta cell - which was highly induced during a 16.7-mM glucose stimulation, via a global activation of islets protein biosynthesis - but also produced an acceleration of the conversion of proinsulin to insulin.

Analysis of Variance↗

PubMed1999

The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats.

Since both the release and de novo biosynthesis of insulin are severely decreased by vitamin D3 deficiency and improved by 1, 25-dihydroxyvitamin D3 (1,25(OH)2D3) repletion following a 6-h delay in the rat, the present experiments investigated the effects of vitamin D3 deficiency on the biosynthesis of heavier molecular weight proteins using electrophoretic separation. Gel protein staining by Coomassie blue showed very different profiles for islets protein production from 4-week vitamin D3-deficient rats compared with normal islets. The pattern was characterised by a decrease in high molecular weight proteins, concomitantly accompanied by an increase in low molecular weight proteins. This tendency was partially reversed in vivo by 1,25(OH)2D3 repletion treatment for 7 days and was evident after only 16 h of treatment. In parallel with these in vivo observations, which represent a static index of islets protein production, a kinetic study was performed in vitro by a double-labelling method allowing us to measure the de novo synthesis of proteins in islets during a strong 16.7 mM glucose stimulation. Comparison of 3H and 14C labelled samples was achieved via coelectrophoresis to avoid experimental artefacts. The study of the ratio of d.p.m. 3H/d.p.m. 14C for each molecular weight protein in islets stimulated by 16.7 mM glucose (versus basal 4.2 mM glucose) showed an increase in the height of certain peaks: 150, 130 and 8.5 kDa. Under the same conditions, islets from 4-week vitamin D3-deficient rats (versus normal islets) presented a large deficit of numerous newly synthesised proteins and particularly those implicated in the response to glucose stimulation. In vitro repletion of 1,25(OH)2D3 tended to reverse, at least in part, the deleterious effect of vitamin D3 deficiency on the de novo protein synthesis of islets but these effects were gradual. Indeed, there was no detectable effect at 2 h incubation, but 1,25(OH)2D3 increased the 60 to 65 kDa, 55 kDa, and 9 to 8 kDa molecular mass proteins at 4 h, and increased the level of most newly synthesised proteins at 6 h. These data support the hypothesis of a beneficial genomic influence of 1,25(OH)2D3 that occurs progressively within the islets of Langerhans and which may prepare the beta cells for an enhanced response to glucose stimulation.

Animals↗

PubMed1998

Vitamin D3 deficiency and alterations of glucose metabolism in rat endocrine pancreas.

After 5 weeks of vitamin D3 deficiency, rats exhibited signs of rachitism, hypocalcaemia and hypoinsulinaemia. As the glucose-induced insulin release process requires calcium and energy production from glucose metabolism within beta cells of Langerhans islets, several steps in the glycolytic pathway and the tricarboxylic acid cycle within beta cells were investigated in vitro. The sensitivity of islets to glucose was studied during incubations in the presence of crescent concentrations of glucose (4.2 to 16.7 mM). Comparison of 50% maximal insulin response showed no modifications induced by vitamin D3 deficiency despite a large fall in the secretory capacity of beta cells. The use of two secretagogues (D-glucose and D-glyceraldehyde) to stimulate insulin release at two different glycolysis steps gave similar responses during perifusions performed in the presence of crescent concentrations of these nutrients, indicating that vitamin D3 deficiency was not a major influence on the first steps in glycolysis. Glucose utilisation by islets, as determined by 3HOH production from D-[5-3H]glucose, was slightly decreased during glucose stimulation of islets from vitamin D3-deficient rats, whereas glucose oxidation inside the tricarboxylic acid cycle, as measured by 14CO2 production from D-[6-14C]glucose, was severely affected. These data, which suggest that vitamin D3 deficiency affects the glycolytic pathway after the D-glyceraldehyde step and mainly alters oxidative events within the tricarboxylic acid cycle, support the hypothesis of an alteration of mitochondrial metabolism.

Animals↗

PubMed1997

Modulatory role of 1,25 dihydroxyvitamin D3 on pancreatic islet insulin release via the cyclic AMP pathway in the rat.

1. Previous studies have shown that vitamin D3 deficiency impairs the insulin response to glucose via an alteration of signal transduction pathways, such as Ca2+ handling and the phosphoinositide pathway. In the present study the adenylyl cyclase pathway was examined in islets from 3 independent groups: normal rats, 4 weeks-vitamin D3 deficient rats and one week-1,25 dihydroxyvitamin D3 (1,25(OH)2D3) treated rats. 2. We found that the very low rate of insulin release observed in vitamin D3 deficient rats could be restored in vitamin D3 deficient islets only with high concentrations of dioctanoyl-cyclic AMP (DO-cyclic AMP), whereas 1,25(OH)2D3 improved the sensitivity of the islets to this exogenous cyclic AMP analogue. 3. The beneficial effect of 1,25(OH)2D3 observed with or without DO-cyclic AMP was protein kinase A-dependent, since the addition of N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulphonamide (H-89), a specific inhibitor of cyclic AMP-dependent protein kinases, decreased the insulin release of treated rats back to the level seen in vitamin D3 deficient islets. 4. The low rate of insulin release could not be consistently related to an alteration in cyclic AMP content of the islets. Indeed, low insulin response to a barium+theophylline stimulus observed in vitamin D3 deficient islets was paradoxically associated with a supranormal cyclic AMP content in the islets. 5. This paradoxical increase in cyclic AMP observed in these conditions could not be attributed to a lower total phosphodiesterase (PDE) activity, although the portion of Ca(2+)-calmodulin-independent PDE was predominant in islets from vitamin D3 deficient rats. 6. On the other hand, the higher cyclic AMP content of vitamin D3 deficient islets could be related to an increase in glucagon-induced cyclic AMP synthesis in relation to the hyperglucagonaemia previously observed in vitamin D3 deficient rats. Since higher concentrations of exogenous glucagon and higher endogenous cyclic AMP concentrations were required in vitro to restore insulin release to normal values, the cyclic AMP-dependent pathways that usually potentiate insulin secretion appeared to be less efficient in relation to an alteration in the post cyclic AMP effector system. 7. 1,25(OH)2D3 exerted a stimulating effect on insulin release via protein kinase A activation but reduced the supranormal cyclic AMP synthesis, thus exerting a differential modulatory influence on biochemical disturbances in islets induced by vitamin D3 deficiency.

Animals↗

PubMed1996

Relationship between calbindin-D28K levels in the A and B cells of the rat endocrine pancreas and the secretion of insulin and glucagon: influence of vitamin D3 deficiency and 1,25-dihydroxyvitamin D3.

The pancreatic B cell is equipped with specific receptors for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and contains vitamin D-dependent calcium binding proteins (calbindin-D). Insulin secretion is impaired by vitamin D deficiency and is restored by 1,25-(OH)2D3 (concomitantly with an improved calcium handling within B cells) but the effect of 1,25-(OH)2D3 on the pancreatic B cell via calbindin-D is unclear. Therefore we examined the relationship between calbindin-D28K or calbindin-D9K and the activity of the endocrine pancreas in normal (N), four week vitamin D-deficient (-D) and one week 1,25-(OH)2D3-replete (+D) rats. Calbindin-D9K was not found in the pancreas, neither in the islets nor in the exocrine part, of any of the groups of rats (N, -D, or+D). Surprisingly, total islet calbindin-D28K content was increased by vitamin D deficiency and partly restored by 1,25-(OH)2D3. Calbindin-D28K immunostaining was observed only on A and B cells in the endocrine part of the pancreas, the greatest staining being found in A cells. This difference in staining density was increased by vitamin D deficiency and decreased by 1,25-(OH)2D3 treatment. In vitro, 1,25-(OH)2D3 also produced a negative influence on calbindin-D28K staining in A cells, as demonstrated using pieces of pancreas incubated with the steroid for 2 h. No significant influence on labeling intensity of B cell calbindin-D28K could be shown. Plasma insulin and islet insulin release in response to 10 mM arginine stimulation were decreased in -D rats and enhanced in +D rats towards N values. In contrast, plasma glucagon and the amount of glucagon secretion, stimulated in vitro by 10 mM arginine or by low (1.7 mM) glucose concentration, was increased in -D rats and attenuated by 1,25-(OH)2D3. Thus there appears to be no relationship between the steady state level of B cell calbindin-D28K and the regulation of insulin secretion by 1,25-(OH)2D3 in vitamin D-deficient rats. However there is a correlation between A cell calbindin-D28K and glucagon secretion, which are both negatively regulated by 1,25-(OH)2D3. The predominance of calbindin-D28K in A cells raises the question as to how A and B cells interact and the role of calbindin-D28K in calcium handling.

Animals↗

PubMed1988

Vitamin D and pancreatic islet function. I. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion.

After weaning, rats were given free access to a control or vitamin D-deprived diet for 2 to 5 weeks. In the vitamin D deficient rats, plasma concentrations of 25-(OH)D3, 1,25-(OH)2D3,24,25-(OH)2D3 calcium, glucose and insulin were all decreased. After an overnight fast, the plasma insulin concentration was also decreased even when the plasma glucose concentration was not significantly affected. The food intake and body growth was also impaired in vitamin D-deficient rats. Administration of vitamin D3 in oil for 3 to 6 days to vitamin D-deficient rats increased the plasma concentration of vitamin D metabolites, calcium and insulin, but not that of glucose, and stimulated food intake and body growth to a larger extent than in rats treated by oil alone. Vitamin D deprivation decreased and vitamin D treatment increased the insulin content of the whole pancreas or isolated islets and the secretory response of the islets to D-glucose. The changes in insulin release remained significant when the hormonal output was expressed relative to the insulin content of the islets. These findings confirm that vitamin D deficiency causes alterations of pancreatic B-cell function. Moreover, the time course for changes in biological variables during vitamin D deprivation and treatment suggests that such an alteration cannot be solely accounted for by concomitant abnormalities in either plasma calcium or glucose concentrations.

Animals↗

PubMed1988

Vitamin D and pancreatic islet function. II. Dynamics of insulin release and cationic fluxes.

Pancreatic islets were prepared from control and vitamin D-deprived rats 2 or 5 weeks after weaning and, in the latter case, after 3 or 6 days treatment with exogenous vitamin D3 (60 nmol per day). The islets were prelabelled with both 86Rb and 45Ca and placed in a perfusion chamber. Vitamin D deprivation or administration failed to affect 86Rb outflow whether prior or after stimulation of the islets by a rise in either extracellular D-glucose or Ca2+ concentration. However, vitamin D deprivation decreased and vitamin D administration enhanced the basal 45Ca fractional outflow rate, as well as the magnitude of changes in both 45Ca and insulin release evoked by the rise in either D-glucose or extracellular Ca2+. It is proposed that the alteration in 45Ca fluxes and insulin release attributable to changes in the supply of vitamin D are, to a large extent, independent of the changes in nutrient catabolism conceivably associated with vitamin D deprivation and administration.

Animals↗

PubMed1987

Effects of constant magnetic fields on the B-cells and insulin target cells in the rat.

Young male rats were exposed to constant uniform magnetic fields of 400 and 800 millitesia (mT). No changes were observed in the body and in the pancreas weight, in the pancreatic insulin content and in the in vitro insulin release of Langerhans islets, in glucose and insulin plasma levels. The magnetic fields abolished the insulin effect on glucose uptake of diaphragms, but not on 1-14C-glucose oxidation. In adipocytes 400 mT increased insulin-stimulated 1-14C-glucose oxidation, when expressed as percentage of mean basal oxidation, and 800 mT diminished it.

Adipose Tissue↗

PubMed1985

Cholinergic stimulation of ion fluxes in pancreatic islets.

Cholinergic agents are known to stimulate the hydrolysis of polyphosphoinositides in pancreatic islets. The effect of carbamylcholine upon ion fluxes in the islet cells was investigated. Carbamylcholine provoked a rapid but poorly sustained increase in 45Ca and 86Rb outflow from perifused islets. Such a cationic response was observed at different glucose concentrations (zero to 16.7 mM), at three concentrations of carbamylcholine (10 microM, 100 microM and 1.0 mM), and in the absence or presence of extracellular Ca2+. It coincided with a biphasic stimulation of insulin release, both the cationic and secretory responses being abolished in the presence of atropine (10 microM). At variance with nutrient secretagogues, carbamylcholine failed to affect the net production of cyclic AMP and caused a transient decrease in 32P outflow from islets prelabelled with [32P]phosphate. It is proposed that cholinergic agents mobilize Ca2+ from intracellular sites, possibly through generation of inositol, 1,4,5-triphosphate from phosphatidylinositol 4,5-bisphosphate. The intracellular redistribution of Ca2+ does not appear sufficient, however, to account fully for the secretory response, which may also involve activation of protein kinase C by diacylglycerol.

Animals↗

PubMed1985

Facilitation of insulin release by N-p-tosylglycine.

N-p-tosylglycine, which inhibits transglutaminase activity in islet homogenates, was found to cause a rapid and sustained facilitation of insulin release evoked by D-glucose, L-leucine or the association of Ba2+ and theophylline in intact islets. Such a facilitating action could not be attributed to any obvious effect upon either nutrient oxidation or 45Ca net uptake and outflow. It failed to be reproduced by glycine, N alpha-p-tosyl-L-arginine methyl ester or N alpha-p-tosyl-L-lysine methyl ester. N-p-tosylglycine (5.0 mM) slightly enhanced insulin release evoked by a high concentration of glucose (16.7 mM) and failed to affect significantly the secretory response to the association of L-leucine and L-glutamine or that of D-glucose and gliclazide. N-p-tosylglycine failed to affect the incorporation of [2,5-3H]histamine in trichloroacetic acid-precipitable material in intact islets. These results suggest that N-p-tosylglycine interferes with a late event in the secretory sequence, possibly at the level of the cell boundary, rather than inhibiting the crosslinking of intracellular proteins.

Acyltransferases↗

PubMed1984

Adrenal interference of insulin secretion after 14-days oestradiol treatment in female rats.

Ovarian-adrenal interactions on insulin secretion during oestradiol treatment were studied in sham-operated, ovariectomized and adrenalectomized-ovariectomized female rats, the latter thus treated to suppress interference from endogenous hormones. Islets of Langerhans isolated from oestradiol or oestradiol + corticosterone treated and control rats were incubated with various glucose concentrations. Oestradiol treatment enhanced basal and glucose stimulated insulin secretion from sham-operated (+12%) or ovariectomized rats (+24%). This effect disappeared in adrenalectomized-ovariectomized rats but reappeared when adrenalectomized-ovariectomized rats were treated with oestradiol + corticosterone (+37%). A 14-day oestradiol treatment had a trophic effect on total protein content independent of adrenal presence (+14%; +15%; +31%; +23% versus respective control groups). Our data demonstrate that corticosterone is necessary for the stimulating effect of oestradiol on insulin secretion.

Adrenal Glands↗

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

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↗