Steroid-induced short term diabetes in chick embryo: Reversible effects ofinsulin on metabolic changes and cataract formation

PURPOSE. TO determine the reversible effect of insulin on glucocorticoid (G C)-induccd cataract formation in relation to systemic metabolic changes in the developing chick embryo. METHODS. Hydrocortisone sodium succinate (HC; 0.25 micromoles) was administ ered to 15-day-old embryos followed by administration of long-acting recomb inant human insulin, 4 and 28 hours later. At the indicated time after HC a dministration, the incidence of cataractous lenses and ally changes in the components of the lenses, liver, and blood were determined. RESULTS. At 48 hours after HC administration, the following observations we re made: opacification of lenses; an elevation of glucose and lipids in the blood and lenses; an increase in lipid peroxide (LPO) in the blood, liver, and lenses; a decrease in glutathione (GSH) in the lens and liver (at 24 h ours after HC administration); and a depletion of adenosine triphosphate (A TP) in the liver. These changes in response to HC administration were rever sed by a double application of insulin. CONCLUSIONS. Insulin antagonizes GC-induced gluconeogenesis, stimulates gly colysis, and ultimately leads to recovery of decreased activity in the citr ic acid cycle. The restoration of ATP by the recovered citric acid cycle ma y facilitate de novo synthesis of GSH, which in turn may diminish GC-induce d elevation of LPO in the liver. Thus, the metabolic changes in response to HC-accelerated gluconeogenesis in the liver, which can be reversed by insu lin, are likely to produce oxidative stress that leads to cataract formatio n. GC-induced metabolic changes in the liver, which are antagonized by insu lin, may relate to production of one of the risk factors for cataract forma tion.