Modulation of β ‐Cell Ouabain‐Sensitive 86 Rb + Influx(Na + /k + Pump) by D‐Glucose, Glibenclamideor Diazoxide

• Published in: Journal of diabetes research 2000-01, Vol.1 (4), p.265-274
• Main Authors: Elmi, Adrian, Idahl, Lars-ÅKe, Sehlin, Janove
• Format: Article
• Language: English
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/EDR.2000.265

The activity of the β ‐cell Na + /k + pump was studied by using ouabain‐sensitive (lmM ouabain) 86 Rb + influx in β ‐cell‐rich islets of Umeå‐ ob/ob mice as an indicator of the pump function. The present results show that the stimulatory effect of glucose on ouabain‐sensitive 86 Rb + influx reached its approximate maximum at 5mM glucose. Pre‐treatment of the islets with 20mM glucose for 60 min strongly reduced the glucose‐induced stimulation of the Na + /k + pump. Pre‐treatment (60 or 180 min) of islets at 0mM glucose, on the other hand, did not affect the magnitude of the glucose‐induced stimulation of 86 Rb + influx dunng the subsequent 5‐min incubation. Glibenclamide stimulated the ouabain‐sensitive 86 Rb + uptake in the same manner as glucose. The stimulatory effect, showed its apparent maximum at 0.5μM. Pre‐treatment (60 min) of islets with 1μM glibenclamide did not reduce the subsequent stimulation of the ouabain‐sensitive 86 Rb + influx. The stimulatory effect of glibenclamide and D‐glucose were not .additive, suggesting that they may have the same mechanism of action. No direct effect of glibenclamide (0.01‐1μM) was observed on the Na + /k + ATPase activity in homogenates of islets. Diazoxide (0.4mM) inhibited the Na + /k + pump. This effect was sustained even after 60 min of pre‐treatment of islets with 0.4mM diazoxide. The stimulatory effect of glibenclamide and D‐glucose were abolished by diazoxide. It is concluded that nutrient as well as non‐nutrient insulin secretagogues activate the Na + /k + pump, probably as part of the membrane repolarisation process.