Steroid-induced short term diabetes in chick embryo: reversible effects of insulin on metabolic changes and cataract formation.
OBJECTIVE
To determine the reversible effect of insulin on glucocorticoid (GC)-induced cataract formation in relation to systemic metabolic changes in the developing chick embryo.


METHODS
Hydrocortisone sodium succinate (HC; 0.25 micromoles) was administered to 15-day-old embryos followed by administration of long-acting recombinant human insulin, 4 and 28 hours later. At the indicated time after HC administration, the incidence of cataractous lenses and any changes in the components of the lenses, liver, and blood were determined.


RESULTS
At 48 hours after HC administration, the following observations were 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 hours after HC administration); and a depletion of adenosine triphosphate (ATP) in the liver. These changes in response to HC administration were reversed by a double application of insulin.


CONCLUSIONS
Insulin antagonizes GC-induced gluconeogenesis, stimulates glycolysis, and ultimately leads to recovery of decreased activity in the citric acid cycle. The restoration of ATP by the recovered citric acid cycle may facilitate de novo synthesis of GSH, which in turn may diminish GC-induced elevation of LPO in the liver. Thus, the metabolic changes in response to HC-accelerated gluconeogenesis in the liver, which can be reversed by insulin, are likely to produce oxidative stress that leads to cataract formation. GC-induced metabolic changes in the liver, which are antagonized by insulin, may relate to production of one of the risk factors for cataract formation.
Watanabe
H
H
Faculty of Pharmaceutical Sciences, Teikyo University, Sagami-ko, Kanagawa, Japan.
Kosano
H
H
Nishigori
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002642:Chick Embryo; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism*; D005938:Glucocorticoids / Q000633:toxicity; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000633:toxicity; D007328:Insulin / Q000494:pharmacology*; D007657:Ketone Bodies / Q000097:blood; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D005938:Glucocorticoids; D007328:Insulin; D007657:Ketone Bodies; D008054:Lipid Peroxides; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D005978:Glutathione; D005947:Glucose; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone