It has been suggested that elevated levels of insulin or insulinlike growth factors (IGFs) play a role in the development of diabetic vascular complications. Previously, we have shown a differential response to insulin between vascular cells from retinal capillaries and large arteries with the former being much more insulin responsive. In the present study, we have characterized the receptors and the growth-promoting effect of insulinlike growth factor I (IGF-I) and multiplication-stimulating activity (MSA, an IGF-II) on endothelial cells and pericytes from calf retinal capillaries and on endothelial and smooth muscle cells from calf aorta.We found single and separate populations of high affinity receptors for IGF-I and MSA with respective affinity constants of 1 X 10-9 M-1 and 10-8 M-l in all four cell types studied.

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A B S T R A C T Glutamate is an inhibitor of phosphate dependent glutaminase (PDG), and renal cortical glutamate is decreased in metabolic acidosis. It has been postulated previously that the rise in renal production of ammonia from glutamine in metabolic acidosis is due primarily to activation of cortical PDG as a consequence of the fall in glutamate. The decrease in cortical glutamate has been attributed to the increase in the capacity of cortex to convert glutamate to glucose in acidosis.In the present study, administration of ammonium chloride to rats in an amount inadequate to decrease cortical glutamate increased the capacity of cortex to produce ammonia from glutamine in vitro and increased cortical PDG. Similarly, cortex from potassium-depleted rats had an increased capacity to produce ammonia and an increase in PDG, but glutamate content was normal. The glutamate content of cortical slices incubated at pH 7.1 was decreased, and that at 7.7 was increased, compared to slices incubated at 7.4, yet ammonia production was the same at all three pH levels. These observations suggest that cortical glutamate concentration is not the major determinant of ammonia production.In potassium-depleted rats there was a 90% increase in the capacity of cortex to convert glutamate to glucose, yet cortical glutamate was not decreased. In vitro, calcium more than doubled conversion of glutamate to glucose by cortical slices without affecting the glutamate content of the slices, and theophylline suppressed conversion of glutamate to glucose yet decreased glutamate content. These observations indicate that the rate of cortical gluconeogenesis is not the sole determinant of cortical glutamate concentration.The increase in cortical gluconeogenesis in acidosis and potassium depletion probably is not the primary Dr. Pagliara performed this work during the tenure of a Daland Fellowship of the American Philosophical Society.Received for publication 5 February 1970 and in revised form 29 June 1970. cause of the increase in ammonia production in these states, but the rise in gluconeogenesis may contribute importantly to the maintenance of increased ammoniagenesis by accelerating removal of the products of glutamine degradation. INTRODUCTIONIn metabolic acidosis there is a rise in renal ammonia production (1, 2), an increase in the capacity of renal cortex to produce glucose from glutamate and other substrates (3), and a decrease in cortical glutamate concentration (4, 5). We and others have suggested that the changes in ammonia production, gluconeogenesis, and glutamate content are causally related (3,4,6). According to this hypothesis, in acidosis the increased conversion of glutamate to glucose is the cause of the fall in cortical glutamate, and since glutamate is an inhibitor of phosphate-dependent glutaminase (4), the fall in glutamate causes activation of this enzyme, thereby increasing ammoniagenesis from glutamine. Consistent with this hypothesis, in metabolic alkalosis both cortical gluconeogenic capacity and ammonia product...