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Arginine metabolism in enterocytes of diabetic rats
Abstract
Diabetic rats and patients exhibit decreased plasma arginine concentrations. Arginine is important in numerous cellular pathways, including the synthesis of nitric oxide and the release of insulin from pancreatic β cells. At present, little is known about the mechanism responsible for the decrease in plasma arginine concentration in diabetics. In adult mammals, enterocytes are the main source of circulating citrulline, which serves as the precursor for arginine synthesis, primarily in the kidney. On the basis that citrulline availability is the rate-limiting factor for renal arginine synthesis, we hypothesized that citrulline synthesis from glutamine was reduced in enterocytes of diabetic rats, which may contribute to the decrease in plasma arginine levels. To test this hypothesis, two experimental series were conducted, which involved the induction of diabetes in Sprague Dawley rats by intravenous administration of streptozotocin. The difference between the experiments lies with the method of insulin administration. In the first experiment, half of the diabetic rats were given two daily subcutaneous injections of insulin within 24 h after the onset of diabetes, and in experiment 2, insulin was administered to half of the diabetic rats through a subcutaneous implantation of a slow-release insulin pellet. In both experiments, half of the diabetic rats did not receive insulin treatment. One month after the onset of diabetes, jejunal enterocytes were prepared from normal, diabetic, and diabetic plus insulin-treated rats. Cells were incubated at 37°C in the presence of 2 mM arginine, 2 mM glutamine, or 2 mM proline plus 2 mM glutamine. Amino acids were quantified by high-performance liquid chromatography. The results indicated that the enterocytes' capability to metabolize arginine, glutamine, and proline is not compromised in the diabetic state. Similarly, argininosuccinate synthase and argininosuccinate lyase activities did not differ among the three groups of rats. These results suggest that the reduced availability of circulating arginine in diabetic rats is not likely due to changes in intestinal citrulline production, intestinal arginine degradation, or renal arginine synthesis. Future studies are necessary to determine whether whole body arginine catabolism is enhanced in diabetic rats due to either an increase in arginase expression, or a decrease in aspartate concentrations, resulting in the decrease in plasma arginine concentrations.
Description
Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.Includes bibliographical references (leaves 42-45).
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Citation
Morrow, Natalie Anne (2002). Arginine metabolism in enterocytes of diabetic rats. Master's thesis, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /ETD -TAMU -2002 -THESIS -M68.
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