Alloxan-induced alteration of insulin release, rubidium efflux and glucose metabolism in rat islets stimulated by various secretagogues.
Insulin release and 86Rb efflux were studied in perifused rat islets exposed in vitro to alloxan (2 mmol/l) 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/l) and markedly delayed the reduction in 86Rb efflux normally produced by the sugar. 3-O-methylglucose (20 mmol/l) provided complete protection against the alteration of 86Rb efflux and partial protection against the inhibition of insulin release. Immediately after alloxan treatment, glyceraldehyde, alpha-ketoisocaproic acid and tolbutamide still induced a rapid release of insulin, but the late phase normally stimulated by glyceraldehyde and alpha-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 alloxan-treated islets and 3-O-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.
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D002208:Caproates / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011188:Potassium / Q000378:metabolism*; D011868:Radioisotopes; D051381:Rats; D012413:Rubidium; D014044:Tolbutamide / Q000494:pharmacology
D002208:Caproates; D007328:Insulin; D011868:Radioisotopes; D005985:Glyceraldehyde; D000496:Alloxan; D014044:Tolbutamide; D005947:Glucose; D012413:Rubidium; D011188:Potassium