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Biomedical subjects

G Somers

Publications and source records attributed to G Somers.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1977

The insulinotropic action of D-erythrose.

D-erythrose (5.0 to 20.0 mM) stimulates insulin release. This insulinotropic action of erythrose displays several features in common with that of glucose. First, erythrose (20 mM) causes a shift to the left of the sigmoidal curve relating the secretory rate to the glucose eoncentration, but fails to enhance the maximal response to glucose. Second, the secretory response to erythrose occurs as an early peak followed by a phase of sustained release. Third, erythrose increases the output of lactate from the islets. Last, erythrose inhibits the efflux of 45calcium and favours its accumulation in isolated islets. It is suggested that, whether in response to glucose or erythrose, an increase in glycolytic flux may represent the key process involved in the identification of the secretagogue, a subsequent remodeling of calcium fluxes being apparently responsible for the activation of the insulin-releasing system.

Animals↗
PubMed1976

Calcium-antagonists and islet function. VI. Effects of barium.

The modality of Ba2+-induced insulin release was investigated in the isolated perfused rat pancreas. The insulinotropic action of Ba2+ was antagonized by Ca2+, Mg2+ and verapamil, and enhanced by EGTA, theophylline, glucose and cytochalasin B. Likewise the net uptake of 133Ba2+ by isolated islets was inhibited by Ca2+, Mg2+ and verapamil. Glucose increased 133Ba2+ net uptake, but only when sufficient Ba2+ had accumulated in the islets. Theophylline failed to affect 133Ba2+ net uptake. These data suggest that (i) Ba2+-induced insulin release is dependent on the accumulation of this cation in the B-cell; (ii) Ba2+ inward transport in the B-cell occurs through a verapamil-sensitive channel characterized by competition between Ba2+, Ca2+ and Mg2+; and (iii) the enhancing effect of theophylline upon insulin release could be due to an intracellular translocation of alkaline-earth cations rather than to an increase in their net uptake. The present findings also support the idea that insulin release can be triggered by the accumulation of suitable divalent cations in a critical site of the B-cell, leading to the activation of a cytochalasin B-response effector system.

Animals↗
PubMed1976

Treatment of diabetic coma with small intravenous insulin boluses.

The clinical efficacy of small intravenous boluses of insulin in treating diabetic decompensation was tested in 23 patients presenting in either a ketoacidotic or a nonketotic diabetic coma. In addition to the usual ionic and fluid replacement, the patients received hourly intravenous injections of insulin 5 IU. This dose lowered blood glucose levels in all but two patients. In the patients who responded the percentage decrease in glycaemia was similar whatever the initial glucose concentration and averaged (+/-SE of mean) 50+/-3% in five hours. Close monitoring of insulin and glucose concentrations after intravenous insulin in three patients showed that despite the short half life of insulin the effect of the intravenous bolus lasted for about 60 minutes. The overall clinical effectiveness of this type of treatment is comparable to that of the other low-dose regimens. Owing to its simplicity, this technique of insulin administration seems most suitable for the routine treatment of diabetic coma.

Blood Glucose↗
PubMed1976

Calcium-antagonists and islet function. IV. Effect of D600.

D600 (2 to 20 muM; alpha-isopropyl-alpha [(N-methyl-N-homoveratril)-gamma-aminopropyl]-3,4,5-trimethoxyphenyl-acetonitril) caused a dose-related, rapid and reversible inhibition of glucose-induced insulin release. It also suppressed the insulinotropic action of a sulphonylurea but failed to affect the enhancing action of theophylline upon glucose-induced release. The inhibitory effect of D600 was enhanced at low extracellular Ca2+ concentration. D600 reduced both basal and glucose-stimulated 45calcium net uptake, whilst failing to affect the efflux of 45calcium from perifused islets. The recognition of glucose by the B-cell was also unaffected by D600 as judged by the effect of the sugar upon both 45calcium efflux and net uptake in the isolated islets. These findings are compatible with the hypothesis that the primary mode of action of D600 is to inhibit Ca2+ entry in the B-cell.

Animals↗
PubMed1976

Calcium-antagonists and islet function. V. Effect of R33711.

R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose and gliclazide but not that of theophylline. A 0.2 muM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process.

Animals↗
PubMed1976

Microsurgery in the prevention of traumatic tattoos.

We were able to remove most of the foreign body particles from a fresh wound caused by a gunpowder blast to the face, using microsurgical techniques. This prevented a subsequent serious dirt tattoo.

Blast Injuries↗
PubMed1976

Calcium antagonists and islet function. II. Interaction of theophylline and verapamil.

Verapamil inhibits glucose-induced insulin release by the isolated perfused rat pancreas. The dose-response relationship for the inhibitory action of verapamil is shifted to higher concentrations of the drug when the concentration of calcium in the perfusate is increased. The degree of inhibition of glucose-induced insulin release by a given concentration of verapamil decreases as the length of exposure to glucose is increased prior to introduction of the calcium antagonist. Theophylline augments glucose-stimulated insulin release and protects the beta-cell against the inhibitory action of verapamil, both effects of theophylline being dose-related. Even after pretreatment of the pancreas with a high concentration of verapamil, theophylline is able, in the presence of glucose, to stimulate insulin release and, eventually, to restore a nearly normal secretory response to this sugar. We suggest that theophylline, by mobilizing calcium from an organelle-bound pool within the beta-cell, compensates for the verapamil-induced reduction in calcium inward transport into the beta-cell.

Animals↗
PubMed1976

Calcium antagonists and islet function. VIII. The effect of magnesium.

Mg2+ in high concentration (10 to 20 mEq/l) caused a dose-related inhibition of glucose-induced 45calcium net uptake and subsequent insulin release in isolated islets. Experiments performed with the isolated perfused pancreas indicated that the inhibitory effect of Mg2+ upon insulin secretion was rapid and reversible. Although excess Mg2+ reduced lactate production by the islets, the process of glucose recognition by the B-cell was apparently unaltered as judged by the inhibitory effect of the hexose upon 45calcium efflux from perifused islets and the resultant accumulation of 45calcium in the islets. Mg2+ in high concentration failed to facilitate 45calcium efflux from the islets, whether in the presence or absence of glucose. These data suggest that the major effect of Mg2+ upon islet function is to inhibit Ca2+ entry in the B-cell.

Animals↗
PubMed1975

One-stage reconstruction for exstrophy of the bladder in girls.

In an African female infant with exstrophy who was a candidate for complete reconstruction of the urinary tract, pelvis, and abdominal wall, the treatment program was simplified by performing iliac osteotomies at the same time as the other repairs, using a single transverse lumbosacral incision for access. A series of 3 wire loops held the symphysis in apposition. A plaster spica, followed by a plaster girdle, minimized the tension on the pubic wires. We believe that we obtained, by this method, superior strength and a better appearance of the abdominal wall and perineum.

Abdominal Muscles↗
PubMed1975

Dynamics of insulin release and microtubular-microfilamentous system. VII. Do microfilaments provide the motive force for the translocation and extrusion of beta granules?

The active role played by beta-cell microfilamentous structures in the dynamics of insulin secretion was investigated by examining the influence of cytochalasin B upon various parameters of hormonal release by the isolated perfused rat pancreas. The view that the cytochalasin-induced changes in insulin release are due to a primary biophysical effect on microfilaments, rather than to an unrelated biochemical alteration of the beta-cell glucose-sensor device, was strengthened by the following observations: (1) the onset and disappearance of the cytochalasin B-induced facilitating action upon insulin release followed a time-course parallel to that characterizing the ultrastructural changes provoked by the drug in the distribution of beta-cell microfilamentous material; and (2) cytochalasin B facilitated leucine-induced insulin release in the presence of a very low glucose concentration. The mold metabolite was also found to transform transient secretory responses into biphasic ones and to prevent the reduction that normally affects the early response to insulinotropic agents when the pancreas is stimulated a few minutes after a prior and short exposure to glucose. The release of insulin evoked by either glucose or gliclazide was abolished in the absence of extracellular calcium, whether in the presence or absence of cytochalasin B. Theophylline and cytochalasin B exerted a synergistic effect upon glucose-induced insulin release. These data support the concept that calcium-dependent contractile events involving cytochalasin B-sensitive microfilamentous structures provide the motive force for both the intracellular translocation and exocytotic release of beta granules.

Animals↗
PubMed1975

Calcium antagonists and islet function. I. Inhibition of insulin release by verapamil.

Verapamil is a potent calcium antagonist known to inhibit excitation-contraction coupling in both myocardium and myometrium. Its effect upon glucose- and sulfonylurea-induced insulin release was investigated in the isolated perfused rat pancreas. After twenty-five minutes' pretreatment and at concentrations ranging between 0.8 and 8.1 muM, verapamil caused a dose-related inhibition of glucose-induced insulin release during both the early and late phase of the secretory process. At a concentration of 0.8 muM, the degree of inhibition was more marked when the exposure time to verapamil prior to stimulation with glucose was increased to sixty minutes. Verapamil also inhibited gliclazide-induced insulin release. Infusion of verapamil during the late phase of the secretory response to glucose demonstrated that the inhibition of insulin release was an immediate and reversible phenomenon. The inhibitory effect of verapamil was enhanced at a subnormal calcium concentration and reduced at a high calcium concentration. These findings are consistent with the well-known calcium dependency of both glucose- and sulfonylurea-induced insulin release and suggest that verapamil might be a promising tool for further studies on the interactions between cations and secretagogues in the beta-cell secretory process.

Animals↗