The effect of allantoin, an active component of yam, on plasma glucose of streptozotocin-induced diabetic rats (STZ-diabetic rats) is investigated. Allantoin decreased plasma glucose levels in a dose-related manner, which was reduced by pretreatment with naloxone or naloxonazine. A concomitant increase in plasma β-endorphin, detected by enzyme-linked immunosorbent assay, was observed. Moreover, allantoin enhanced β-endorphin release from the isolated adrenal medulla of STZ-diabetic rat in a dose-related manner. However, its plasma glucose lowering action was reduced but not totally abolished by bilateral adrenalectomy. Furthermore, allantoin directly increased radioactive glucose uptake in isolated skeletal muscle, and repeated administration for 3 days increased GLUT4 mRNA and protein levels in muscle. This effect was markedly reduced in STZ-diabetic rats with bilateral adrenalectomy. This study suggests that allantoin increases GLUT4 gene expression in muscle by increasing β-endorphin secretion from the adrenal gland in STZ-diabetic rats.
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