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The role of reduced glucose transporter content and glucose metabolism in the immature secretory responses of fetal rat pancreatic islets

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Summary

Isolated fetal islets show an immature or poor secretory response to nutrient secretagogues which may result from impaired mitochondrial oxidative processes. Insulin secretion, glucose metabolism and detection of metabolic enzymes by radiolabelling and immunoprecipitation were compared in islets isolated from neonatal (aged 5 days) and fetal rats (at 20 days gestation). The insulin secretory dynamics of fetal islets were abnormal in response to stimulation by glucose (10 mmol/1); a rapid release of insulin reaching a maximum 6 min after stimulation was observed with no rising second phase release. However, when the data were expressed as percentage of islet insulin content released, fetal islets released significantly more insulin than neonatal islets in response to glucose (4.86 ± 0.45 % vs 1.81 ± 0.62 %, p < 0.01) or 100 nmol/1 glibenclamide (2.49 ± 0.17% vs 0.25 +- 0.06 %, p < 0.001). Fetal islets however, failed to release insulin in response to stimulation by glyceraldehyde (10 mmol/1) unlike neonatal islets. Both glucose utilisation (as measured by the formation of [3H] H2O from 5-[3H] glucose) and glucose oxidation (as measured by the formation of [14C] CO2 from U-[14C] glucose) did not increase significantly in response to increasing the medium glucose concentration to 10 mmol/1 whereas in neonatal islets, glucose utilisation and glucose oxidation were significantly increased 2.5- and 2.7-fold, respectively. When islets were incubated with both radiolabelled glucoses simultaneously, the rate of glucose oxidation was shown to be directly proportional to the rate of glucose utilisation. The relationship between glucose utilisation and glucose oxidation was similar in fetal and neonatal islets. Finally, in experiments to detect and semiquantify metabolic enzymes, the level of GLUT-2 transporter protein was significantly reduced by 50 % (p < 0.02) whereas the levels of pyruvate dehydrogenase peptides were similar in fetal and neonatal islets. In conclusion, these data do not support the hypothesis that abnormal mitochondrial oxidation is responsible for the immature secretory responses to nutrient secretagogues found in fetal islets but rather that step(s) earlier in the glycolytic pathway are important for development of normal secretory function.

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  1. Division of Basic Medical Science, St. Mary’s Hospital Medical School, Imperial College, London, UK

    S. J. Hughes

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Hughes, S.J. The role of reduced glucose transporter content and glucose metabolism in the immature secretory responses of fetal rat pancreatic islets. Diabetologia 37, 134–140 (1994). https://doi.org/10.1007/s001250050083

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  • DOI: https://doi.org/10.1007/s001250050083

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