In previous experimental studies we have found a 47% incidence of congenital cataracts among the fetuses of manifestly diabetic (MD) rats, and 4% of the offspring of normal (N) rats. The aim of the present study was to clarify the role of the sorbitol shunt in the pathogenesis of this congenital defect. Light microscopical evaluation of the fetal lenses revealed excessive formation of vacuoles in offspring of MD rats compared to N offspring. On gestational day 16 we found that aldose reductase (AR) activity was doubled in the lenses of fetuses of MD rats as compared to that of N fetuses. This difference as well as the net activity of AR declined in both groups during subsequent development. The sorbitol concentration was elevated more than ten-fold in the MD fetal lenses compared to N fetal lenses at all time points. The sorbitol concentration in both the MD and the N group decreased from day 16 to day 20 and increased again slightly on day 22. We conclude that the diabetic uterine milieu induces elevated AR activity and sorbitol formation in the fetal lens. This over-activity of the sorbitol shunt may produce metabolic and osmotic imbalances in the fetal lens, resulting in excessive vacuole formation and subsequent development of congenital cataract.
Calcium re-absorption in the kidney is impaired in streptozotocin (STZ) diabetic rats, thereby causing hypercalciuria. Increased calcium loss starts within 1-2 days after induction of diabetes and reaches a plateau after 2 weeks. The excessive calcium excretion was previously shown to be reduced by treatment with gamma-linolenic acid (GLA) or evening primrose oil rich in GLA. However, in these studies, the animals were pre-treated for several weeks before injection of STZ. In the present study we investigated whether GLA can reduce calcium excretion when treatment starts at the same time as induction of diabetes. Rats were made diabetic with 60 mg/kg STZ and at the same time food was fortified with 0.4% GLA for the treatment group. A control group was treated with vehicle alone and given standard feed only. Urine was collected from animals in metabolism cages every 3rd day for a period of 26 days. The diabetic group increased their food and water consumption, and urine and faeces production as compared to the control group. The urinary loss of Ca, Mg, Zn, Na, K and creatinine was markedly increased in the diabetic group as compared to the control. GLA treatment, however, did not affect any of these variables. Analysis of fatty acids in kidneys of the rats showed an increased concentration of GLA in the treated group as compared to the two non-treated groups. We conclude that GLA treatment must commence before STZ injection in order to attenuate diabetes-induced hypercalciuria.
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