Triiodothyronine Production by the Perfused Rat Kidney Is Reduced by Diabetes Mellitus but Not by Fasting*

The effects of fasting and streptozotocin-induced diabetes on renal T3 production were studied in the isolated perfused rat kidney. Kidneys were perfused for 1 h at 37 C and pH 7.4 with two perfusion media, containing different oncotic agents (BSA and a modified collagen product, Haemaccel) and with widely varying free T4 concentrations [15.6 ng/dl (200 pM) in BSA, 132 ng/dl (1703 pM) in Haemaccel]. Basal kidney T3 concentrations fell by 65.3 +/- (SE) 5.2 and 56.4 +/- 3.4% of control in fasted and diabetic rats, respectively, in parallel with similar decreases in serum T3 concentrations. Fasting did not alter T3 production, T4 uptake, or the conversion of T4 to T3 in the perfused kidney. In contrast, diabetes decreased renal T3 production by 43.7 +/- 5.4% (P less than 0.001) and 31.2 +/- 3.5% (P less than 0.005) from control when perfused with BSA and Haemaccel, respectively. This decline in T3 production was the result of an insulin-reversible decrease in the conversion of T4 to T3, whereas T4 uptake was unchanged. Kidneys from diabetic rats retained more of the T3 produced than did kidneys from control rats, and this was also reversed with insulin treatment. These studies demonstrate significant differences in the metabolism of T4 and disposition of the T3 generated in the kidneys of fasting and diabetic rats. In both fasting and diabetes, T4 metabolism in the kidney was qualitatively and quantitatively different than that previously observed in the perfused liver. We postulate that decreased sensitivity or exposure to intraportal hormones and/or metabolites may explain these differences.