Effect of Alloxan on Permeability and Hexose Transport in Rat Pancreatic Islets

McDaniel, Michael L.; Anderson, Stasia A.; Fink, Jill L.; Roth, C.; Lacy, Paul E.

doi:10.1210/endo-97-1-68

Cited by 36 publications

(22 citation statements)

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“…Such an effect of aUoxan was not found in islets of ob/ob mice [6], probably because measurements of the amount of 86Rb retained in the tissue are not sensitive enough to detect a transient increase in 86Rb efflux. Although this increase in K-permeability could conceivably be the result of damage to the cell membrane, several arguments do not support this possibility: (a) the effect is transient even when alloxan is present for 15 min; (b) it is not accompanied by a leak of insulin in our system; (c) a similar dose of aUoxan does not augment the permeability of rat islet cell membranes to sucrose [9]; and (d) it is quickly reversed by glyceraldehyde, tolbutamide and aketoisocaproic acid. We would suggest rather that the blockade [6] of an electrogenic Na/K pump [27] is, at least partially, the cause of the depolarization measured in alloxan treated B-cells [5] and that the increase in 86Rb efflux is the consequence of this fall in membrane potential.…”

Section: Effect Of Alloxan On Rubidium Effluxmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

“…3-0-Methylglucose protects against this deleterious effect, which cannot be accounted for by a reduced glucose transport in islet cells [9]. An impairment of glucose oxidation by mouse islets has also been reported after in vivo treatment of the animals with alloxan [29] or in vitro exposure of the islets to the drug [30].…”

Section: Effect Of Alloxan On Glucose Metabolismmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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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Section: Effect Of Alloxan On Rubidium Effluxmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Alloxan On Glucose Metabolismmentioning

confidence: 99%

mentioning

confidence: 99%

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

1979

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“…The following evidences made glucose receptor hypothesis a more permissible one; i) alloxan did not inhibit hexose transport nor metabolism in the pancreatic islets (McDaniel, et al, 1975), ii) alloxan inhibition of glucose-induced insulin release was reversed by concomitant presence of -anomer of D-glucose (Niki , et al, 1975;McDaniel, et al, 1976).…”

Section: In1974mentioning

confidence: 99%

Alloxan inhibits glucose oxidation in the pancreatic islets.

et al. 1979

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SynopsisThe effects of alloxan on glucose oxidation and the protection by anomers of D-glucose from alloxan inhibition of glucose oxidation in the pancreatic islets were investigated using in vitro incubation of rat isolated islets.The pretreatment by alloxan (5-30mg/dl) for6minutes inhibits significantly14CO2 formation from 14C-U-D-glucose (10mM) and the addition of a-anomer of D-glucose (8.3mM) to alloxan (20mg/dl) completely reverses alloxan inhibition of glucose oxidation.These findings seem to be incompatible with the recent view that alloxan acts at the glucose receptor on the plasma membrane of pancreatic without affecting glucose metabolism in the pancreatic islets.

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The Physiology of Insulin Release

Lacy

1977

The Diabetic Pancreas

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Effect of Alloxan on Permeability and Hexose Transport in Rat Pancreatic Islets

Cited by 36 publications

References 1 publication

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

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

Alloxan inhibits glucose oxidation in the pancreatic islets.

The Physiology of Insulin Release

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