THYROXINE METABOLISM IN DIABETIC RATS

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Abstract
The metabolism of thyroxine (T4) was determined in untreated and in insulin-treated diabetic rats. Male Wistar rats weighing approximately 200 g were made diabetic by the i.p. administration of streptozotocin (6.5 mg/100 g body weight) and 17 of those with blood sugar levels above 500 mg/100 ml were studied. In addition, 11 insulin-treated diabetic and 18 control rats were investigated. All the animals were injected i.v. with a tracer dose of [125I]T4 (1 .mu.Ci and 0.015 .mu.g). After this blood samples were obtained by cardiac puncture at 16, 24, 40 and 48 h. The 24 h urinary excretion of inorganic 125I was also determined. The parameters of T4 metabolism were obtained by the least squares method and by an extrapolation technique. In untreated diabetic rats the fractional T4 turnover was 4.4%/h, the distribution space 36.7 ml/100 g body weight, metabolic clearance 1.57 ml/100 g per h and urinary clearance 0.33 ml/100 g per h. The 24 h urinary excretion of 125I was 21.3% of the injected radioactivity. Of these values the distribution space (P < 0.001) and metabolic clearance (P < 0.05) were significantly increased above those in the control animals. In insulin-treated rats all parameters were within normal values. Among these groups the serum T4 concentration was measured in 6 control, 5 untreated diabetic and 6 insulin-treated animals. The untreated diabetic animals had a significantly decreased serum T4 level but this was balanced by an enlarged distribution space so that the final hormone degradation was normal. The T4 binding activity of serum was assessed by th in vitro red cells uptake of [125I]T4 and by determining the proportion of serum free T4. Both these indices indicated a decrease in serum binding activity in the diabetic animals. The data suggest that the fall in serum T4 levels observed in the untreated diabetic rats was the result of decreased plasma binding of T4 and an increase in distribution space precipitated by lack of insulin.