The coupling of metabolic to secretory events in pancreatic islets. The possible role of glutathione reductase.
The participation of glutathione reductase in the process of nutrient-stimulated insulin release was investigated in rat pancreatic islets exposed to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU caused a time-and dose-related, irreversible inhibition of glutathione reductase activity. This coincided with a fall in both GSH/GSSG ratio and the thiol content of the islets. Pretreatment of the islets with BCNU inhibited the oxidation of glucose and its stimulant action upon both 45Ca net uptake and insulin release. Although BCNU (up to 0.5 mM) failed to affect the oxidation of L-leucine and L-glutamine, it also caused a dose-related inhibition of insulin release evoked by the combination of these two amino acids. The latter inhibition was apparently not fully accounted for by the modest to negligible effects of BCNU upon 45Ca uptake, 45Ca efflux, 86Rb efflux and cyclic AMP production. Since BCNU failed to inhibit insulin release evoked by the association of Ba2+ and theophylline, these results support the view that glutathione reductase participates in the coupling of metabolic to secretory events in the process of nutrient-stimulated insulin release. However, the precise modality of such a participation, for example the control of intracellular Ca2+ distribution, remains to be elucidated.
Malaisse
W J
WJ
Dufrane
S P
SP
Mathias
P C
PC
Carpinelli
A R
AR
Malaisse-Lagae
F
F
Garcia-Morales
P
P
Valverde
I
I
Sener
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002330:Carmustine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005973:Glutamine / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D007930:Leucine / Q000494:pharmacology; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats
D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D005973:Glutamine; D019344:Lactic Acid; D019289:Pyruvic Acid; D000242:Cyclic AMP; D005980:Glutathione Reductase; D005978:Glutathione; D007930:Leucine; D002118:Calcium; D002330:Carmustine