Diazoxide-induced long-term hyperglycemia. II. Slackening of proinsulin conversion.
The rate of glucose-stimulated insulin release was found to be increased but that of proinsulin conversion decreased in islets removed from diazoxide-treated rats. This coincided with an elevated islet proinsulin/insulin ratio. The defect in proinsulin conversion was not corrected by preincubating the islets, at high glucose concentration, in the presence of either urokinase or rat serum. Likewise, the administration of kallikrein inhibitor in vivo did not affect the rate of proinsulin conversion as measured in vitro. Since these results fail to document a role for exocytosis-coupled endocytotic uptake of circulating factors in the efficiency of proinsulin conversion, it is speculated that the slackening of the latter process in islets removed from diazoxide-treated rats could be somehow linked to sustained inhibition of insulin release.
Valverde
I
I
Fundacion Jimenez Diaz, Centro Associado al Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Alarcon
C
C
Rovira
A
A
Malaisse-Lagae
F
F
Malaisse
W J
WJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011384:Proinsulin / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D007328:Insulin; D011384:Proinsulin; D014568:Urokinase-Type Plasminogen Activator; D003981:Diazoxide