The kinetics of lactate and pyruvate (1 and 5 mM in each case) metabolism was studied in isolated dog renal tubules. Utilization of these two substrates and the production of glucose, pyruvate, or lactate, and alanine were determined. The rates of lactate and pyruvate utilization and of glucose production were constant during 60 min of incubation. Glucose production from pyruvate was less than that from lactate. Addition of albumin to the incubation medium greatly inhibited lactate and pyruvate utilization at both substrate concentrations. It stimulated, however, glucose production from 1 mM, but not 5 mM, lactate or pyruvate. These effects were found to be due to the presence of fatty acids in the albumin solution used. In the absence of fatty acids, glucose production represented 35 to 40% of lactate uptake, but represented less than 20% of pyruvate uptake. Fatty acids markedly enhanced the percentage of transformation of lactate and pyruvate into glucose, and that of pyruvate into lactate. Alanine represented 20% or less of lactate and pyruvate uptake. These results suggest that fatty acids have a regulatory influence on lactate and pyruvate dog kidney metabolism.

Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p less than 0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6 +/- 10% vs 2.3 +/- 2%, p less than 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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