The serum concentration of ketones increases in both fasting and diabetic ketoacidosis. Whether ketones alter, independent of changes in pH, in number and affinity of insulin receptors is not known. The binding of insulin 125I by 24 X 10(6)IM-9 lymphocyte cells was examined in both the presence and absence of 8 mM beta-OH butyrate. Studies were conducted at multiple concentrations of insulin. A consistent increase of insulin binding was induced by beta-OH butyrate. The mean maximum increase of insulin binding was 35%, which achieved significance at the 1% level.

The binding of insulin to a specific receptor on IM-9-cultured human lymphocytes was studied in vitro under conditions simulating diabetic ketoacidosis. Compared with control incubations at pH 7.4, binding was reduced by 19 per cent at pH 7.1 and by 48 per cent at pH 6.8. Addition of beta-hydroxybutyrate, at concentrations similar to those seen clinically, "restored" insulin binding toward normal. We suggest that, by counteracting the effects of acidosis, ketoacids themselves maintain normal insulin-receptor binding in diabetic ketoacidosis. These data also illustrate that small molecules, present in vivo, can significantly alter the interactions between a hormone and its receptor in vitro.

The thyroid hormones triiodothyronine (T3) and L-thyroxine appear to enhance regeneration in the peripheral and central nervous system (CNS). The following experiments examine possible metabolic substrates for the action of T3 on the adult rat CNS after spinal hemisection. The protein incorporation of (3H)lysine after a left spinal hemisection (T2) or control operations was examined 1, 3, 7, and 14 days postoperation. Triiodothyronine (1 microgram/kg body weight in a bicarbonate buffer) was injected daily for the postoperation or equivalent time period. One hour prior to decapitation, animals were given a subcutaneous injection of 200 microCi of (3H)lysine. Samples of brain and spinal cord were dissolved, and the radioactivity of acid-precipitable protein and acid-soluble fractions were determined by scintillation counting. T3 treatment influenced the general levels of incorporation of all treated groups over all days postoperation. Specific effects were observed in spinal hemisected T3-treated animals. A significant hemispheric (P less than 0.05) asymmetry was present at 3 days postoperation with the right somatomotor cortex higher in protein radioactivity than the left. In spinal cord, the area of the lesion and areas just caudal to the lesion were higher in (3H)lysine incorporation in T3-treated rats relative to controls. T3 effects appear to involve an increased sensitivity of the cells of the injured nervous system to the hormone.