Vitamin A status affects the plasma parameters and regulation of hepatic genes in streptozotocin-induced diabetic rats

Abstract

Vitamin A (VA) status regulates metabolism in rats. Whether VA status and availability of retinoic acid (RA) contribute to the insulin-regulated hepatic gene expression remains to be determined. Zucker lean rats with VA sufficient (VAS) or VA deficient (VAD) status were treated with streptozotocin (STZ) to induce insulin-dependent diabetes. They were treated with saline (STZ-VAS-C or STZ-VAD-C), RA (STZ-VAS-RA or STZ-VAD-RA), insulin (STZ-VAS-INS or STZ-VAD-INS), or insulin + RA (STZ-VAS-INS + RA or STZ-VAD-INS + RA) for 3 h. Insulin and insulin + RA treatments reduced tail tip blood glucose, raised plasma insulin and suppressed plasma β-hydroxybutyrate levels in both STZ-VAD and STZ-VAS rats. STZ-VAD-INS and STZ-VAD-INS + RA rats had lower plasma glucose levels than STZ-VAD-C rats had. STZ-VAD-INS and STZ-VAD-INS + RA rats had higher plasma leptin level and lower glucagon level than STZ-VAD-C rats did. Insulin treatment induced Gck, Srebp-1c and Fas and suppressed Pck1 expression levels in the liver of STZ-VAS and STZ-VAD rats. Interestingly, insulin treatment inhibited Cyp26a1 expression in STZ-VAD, but not STZ-VAS rats, whereas RA treatment induced it in both. RA treatment induced Gck expression only in STZ-VAD rats. Insulin + RA treatment further induced the Cyp26a1 and Gck expressions in STZ-VAD rats. The Srebp-1c expression levels of STZ-VAD-INS and STZ-VAD-INS + RA rats were higher than that of STZ-VAS-INS and STZ-VAS-INS + RA rats. The changes of Gck mRNA and glucokinase protein were consistent. In STZ-induced diabetic rats, VA is not required for insulin-regulated Gck, Srebp-1c, Fas and Pck1 expression. However, VA status altered responses of certain genes (Cyp26a1 and Srebp-1c) to insulin treatment.