It has been reported in the USA and Korea since 1975 that Vacor®, rodenticide, containing N-3-pyridylmethyl N'-p-nitrophenyl urea causes insulin-dependent diabetes mellitus. The pathomechanism of Vacor®-induced diabetes mellitus has yet to be clarified. The effect of Vacor®, therefore, was studied in terms of insulin release from isolated rat pancreatic islets. Vacor® suppressed glucose-stimulated insulin release, but did not affect the insulin release induced by theophylline or 12-o-tetra-decanoylphorbol 13-acetate. It was suspected that the suppression of insulin release from pancreatic islets by Vacor® may contribute to the pathomechanism of Vacor®-induced diabetes mellitus and that this suppression might not be related to cAMP anc C-kinase.
Stable transfectants in Chinese hamster ovary cells that express the protein encoded by human insulin-like growth factor I (IGF-I) receptor cDNA (CHO. IGFIR cells) were tested for the stimulatory effect of IGF-I on poly (glu-tyr) phosphorylation and glycogen synthesis. Using 32P-ATP, IGF-I stimulated the incorporation of 32P into poly (gly-tyr) in a dose-dependent manner. IGF-I also stimulated glycogen synthesis in this cell line, while much less stimulation was observed in parental CHO cells. These results indicate that the human IGF-I receptor on this cell line is functional and thus likely to be a useful tool in studying the role of IGF-I receptor.
Glucocorticoid is known to increase insulin receptor mRNA, but it is unclear whether or not this effect is mediated through the glucocorticoid receptor. In this study, by using RU 38486, which has a strong affinity for glucocorticoid receptors without exerting any glucocorticoid-like action, we investigated how dexamethasone affects insulin receptor mRNA levels in IM-9 cells. The following results were obtained: 1) After 24 hours of culture, dexamethasone (10-6M) significantly increased insulin receptor mRNA levels in IM-9 cells. 2) In a dose-dependent manner (10-8-10-10M), RU 38486 markedly inhibited the effects of dexamethasone (10-6M) on insulin receptor mRNA levels. 3) There were no significant changes in insulin receptor mRNA levels in IM-9 cells cultured with RU 38486 (10-8M) alone. These results suggest that dexametasone increases insulin receptor mRNA after binding to its receptor at least in cultured IM-9 cells.