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 < 0.001) and 31.2 ± 3.5% (P < 0.005) from control when perfused with BSA and Haemacciil, respectively. This decline in T₃ production was the result of an insulin-reversible decrease in the conversion of T₄ to T₃, where is T₄ uptake was unchanged. Kidneys from diabetic rats retained more of the T₃ produced than did kidneys from control rats, ai id 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 t le 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.