Evidence for a Direct Action of Insulin to Increase Renal Reabsorption of Calcium and for an Irreversible Defect in Renal Ability to Conserve Calcium Due to Prolonged Absence of Insulin

Male rats were injected with streptozotocin (STZ), 60 mg/kg, i.p., on 2 successive days. Six hours after the last STZ injection, some STZ-diabetic rats began receiving daily injections of insulin that were insufficient to control blood glucose. Another group of STZ-diabetic rats received insulin injections after 2 wk duration of untreated diabetes. Still other STZ-diabetic rats received no insulin treatment. Under sodium pentobarbital anesthesia, kidneys from each treatment group were isolated and perfused with an artificial“plasma”containing ⁴⁵Ca. As urine was collected, urine-to-per-fusate ultrafiltrate (U/P) ratios for ⁴⁵Ca were determined. The results of the studies showed that: STZ diabetes reduced ⁴⁵Ca reabsorption by the kidney; the increased urinary excretion of calcium was not due to an osmotic effect or to a direct nephrotoxic action of STZ; and insulin therapy instituted early, but insufficient to control blood glucose, reduced the diabetes-induced calcium loss via a direct action on the kidney, whereas insulin therapy instituted late failed to reverse renal loss Of calcium.