Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity.

Dean, Philip M.; Matthews, E. K.; Sakamoto, Yuzuru

doi:10.1113/jphysiol.1975.sp010899

Cited by 90 publications

(51 citation statements)

References 34 publications

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“…Since the hyperpolarization stabilized at an estimated value close to EK it can be suggested that KATP channels were activated by removal of glucose. To our knowledge this is the first report demonstrating hyperpolarization by glucose deprivation in a cell type other than the pancreatic â_cells (Dean, Matthews & Sakamoto, 1975;Ashcroft, Ashcroft & Harrison, 1988) and the glucose-sensitive neurons (Ashford, Boden & Treherne, 1990). Since hyperpolarization induced by glucose removal was observed in pyruvate-containing as well as pyruvate-free solutions, the ATP generated by pyruvate oxidation in the mitochondria apparently did not affect the activity of KATP channels.…”

Section: Hyperpolarization Induced By Glucose Deprivationmentioning

confidence: 88%

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation

Langheinrich

Daut

1997

The Journal of Physiology

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The present study was designed to test if microvascular coronary endothelial cells express ATP–sensitive K+ channels (KATP channels). We performed microfluorometric measurements of the membrane potential of freshly isolated guinea‐pig coronary capillaries equilibrated with the voltage–sensitive dye bis‐oxonol (bis‐[1,3–dibutylbarbituric acid] trimethineoxonol, [DiBAC4(3)]). The resting membrane potential of capillaries in physiological salt solution was −46±4.2 mV (n= 8) at room temperature (22 °C) as determined after calibration of the fluorescence using the Na+–K+ ionophore gramicidin in the presence of different K+ concentrations. Spontaneous membrane potential fluctuations of 10–20 mV amplitude were often observed. A reversible, sustained hyperpolarization to a new membrane potential close to the K+ equilibrium potential (EK) could be induced by application of the K+ channel openers HOE 234 (100 nm to 1 μM), diazoxide (10 pm to 100 nM) or pinacidil (100 nM). Subsequent addition of glibenclamide (200 nm to 2 μM) reversed this hyperpolarization. A glibenclamide–sensitive hyperpolarization of coronary capillaries to values near EK was also observed upon omission of D‐glucose (10 mM) from the superfusing solution or by substituting L‐glucose for D‐glucose. Maximum hyperpolarization was reached in less than 10 min. Our results suggest that microvascular coronary endothelial cells express KATP channels which may be activated during hypoglycaemia.

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Section: Hyperpolarization Induced By Glucose Deprivationmentioning

confidence: 88%

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation

Langheinrich

Daut

1997

The Journal of Physiology

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“…For instance, an arrest of the Na/K pump can theoretically be the cause as well as the consequence of decreased metabolism. However, the depolarization of B-cells produced by alloxan is not expected to result from an impaired energy production, since classical uncouplers or inhibitors of glucose metabolism hyperpolarize B-cells [12,28]. A direct effect of alloxan on the Na/K pump is thus plausible [6].…”

Section: Effect Of Alloxan On Rubidium Effluxmentioning

confidence: 99%

Alloxan-induced alteration of insulin release, rubidium efflux and glucose metabolism in rat islets stimulated by various secretagogues

1979

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Summary.Insulin release and 86Rb efflux were studied in perifused rat islets exposed in vitro to alloxan (2 mmol/1) for 5 min. At a low glucose concentration, alloxan transiently increased 86Rb efflux. Alloxan immediately and completely abolished the secretory response to glucose (15 mmol/1) and markedly delayed the reduction in 86Rb efflux normally produced by the sugar. 3-0-methylglucose (20 mmol/ 1) provided complete protection against the alteration of 86Rb efflux and partial protection against the inhibition of insulin release. Immediately after alloxan treatment, glyceraldehyde, ct-ketoisocaproic acid and tolbutamide still induced a rapid release of insulin, but the late phase normally stimulated by glyceraldehyde and a-ketoisocaproic acid was inhibited. If islets were exposed to glyceraldehyde or tolbutamide 15 min after alloxan treatment, the rapid insulin release was also markedly impaired. Alloxan failed, however, to affect the ability of these three stimuli to reduce 86Rb efflux from islet cells. Glucose oxidation and utilization were decreased in alloxantreated islets and 3-0-methylglucose protected against this effect. The results show that the glucose recognition system in B-cells is the most rapidly and severely affected by alloxan. The drug also alters the response to other secretagogues, the insulin releasing properties of which can be impaired without alteration of their ability to reduce 86Rb efflux.Key words: Isolated rat islets, alloxan, perifusion, insulin release, rubidium efflux, glucose metabolism, glucose, glyceraldehyde, a-ketoisocaproic acid, tolbutamide.Alloxan has been widely used to induce experimental diabetes [1], but the exact mechanisms by which the drug produces a relatively selective destruction of pancreatic B-cells remain elusive. Elucidation of the molecular mechanisms of its action would certainly be of more than pharmacological interest. Indeed, observations that glucose can protect B-cells against alloxan toxicity [2, 3] make the drug a potential probe of the physiological stimulus-secretion coupling.Present experimental evidence, recently discussed in detail [4], suggests that the B-cell membrane may be an important site of the action of alloxan. In mouse islets alloxan produces depolarization of Bcells [5] and inhibition of the univalent cation pump [6]. In rat islets it produces a loss of membraneassociated particles [7]. In toadfish islets [8], but not in rat islets [9], it increases the membrane permeability to mannitol, which is normally restricted to the extracellular space.Recent studies have shown that glucose rapidly and markedly decreases potassium efflux from rat islet cells [10]. This supports the suggestion [11] that the depolarization of B-cells produced by the sugar [12-13] might be due to a reduction in K-permeability. The importance of these changes in K-permeability is underlined by the evidence that pharmacological agents which potentiate the effect of glucose on K-permeability also potentiate its insulin releasing effect, whereas those which augment...

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“…The latter concept was already proposed as a working hypothesis by several investigators (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

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

Sener¹,

Hutton²,

Kawazu³

et al. 1978

J. Clin. Invest.

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A B S T R AC T 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 insulin secretion. NH4 failed to affect glucose utilization and oxidation, glucose-stimulated proinsulin biosynthesis, the concentration of ATP, ADP, and AMP, and the intracellular pH. NH4+ also failed to affect the ability oftheophylline and cytochalasin B to augment glucoseinduced insulin release. However, in the presence and absence of glucose, accumulation of NH4+ in islet cells was associated with a fall in the concentration ofNADH and NADPH and a concomitant alteration of "Rb+ and 45Ca2+ (or 133Ba2+) handling. These findings suggest that reduced pyridine nucleotides, generated by the metabolism of endogenous or 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.

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Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity.

Cited by 90 publications

References 34 publications

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation

Alloxan-induced alteration of insulin release, rubidium efflux and glucose metabolism in rat islets stimulated by various secretagogues

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

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Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity.

Cited by 90 publications

References 34 publications

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K+ channel openers and glucose deprivation

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K+ channel openers and glucose deprivation

Alloxan-induced alteration of insulin release, rubidium efflux and glucose metabolism in rat islets stimulated by various secretagogues

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

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Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation

Hyperpolarization of isolated capillaries from guinea‐pig heart induced by K⁺ channel openers and glucose deprivation