Immature mitochondrial oxidative phosphorylation in fetal rat pancreatic islets — ASN Events
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Immature mitochondrial oxidative phosphorylation in fetal rat pancreatic islets (#243)

Jian Tu 1 , Bernard E Tuch 2 , David R Thorburn 3
  1. Diabetes Transplant Unit, Prince of Wales Hospital, Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia
  2. Diabetes Transplant Unit, Prince of Wales Hospital, now at CSIRO Materials Science and Engineering, Sydney, NSW, Australia
  3. Murdoch Children’s Research Institute, Melbourne, VIC, Australia

We tested the hypothesis that glucose-unresponsive insulin secretion from fetal rat islets was related to inadequate ATP synthesis caused by immature oxidative phosphorylation in mitochondria.  We found that the rate of glucose oxidation was significantly less in islets isolated from the fetal rat at 21-day gestational age than in adult islets.  Enzyme activities of the individual respiratory chain complexes I (rotenone-sensitive NADH:CoQ1 oxidoreductase), II (succinate:CoQ1 oxidoreductase), II+III (succinate:cytochrome c oxidoreductase), III (decylbenzylquinol:cytochrome c oxidoreductase), and IV (cytochrome c oxidase) were less in mitochondrial fractions prepared from the fetal islets, in the range of 5 - 74% of adult values.  Among them, complex III, a key component of the electron transport chain was only 5% of the adult value.  ATP synthesis in permeabilized fetal islets was 23% of the adult value for ADP+malate/pyruvate-dependent respiration.  The ATP level in the fetal islets was less than that of their adult counterpart, while ADP and AMP levels were greater, which resulted in low ratios of ATP/ADP (0.16 vs 2.54, P<0.001) and ATP/(ADP+AMP) (0.15 vs 2.13, P<0.001).  To determine whether glucose had any effect on the ATP/ADP and ATP/(ADP+AMP) ratios, islets were exposed to different concentrations of glucose for 30 min.  With increasing concentrations of glucose, ATP/ADP and ATP/(ADP+AMP) increased to a lesser extent in the fetal islets, and could not initiate glucose-induced insulin secretion.  In conclusion, mitochondrial oxidative phosphorylation in the fetal rat islets is immature resulting in a low capacity of ATP synthesis.  This and a large ADP and AMP pool result in failure to increase the ATP/ADP and ATP/(ADP+AMP) ratios sufficiently to complete glucose stimulation-secretion coupling.