title: Enhanced glucose homeostasis in BHE/cdb rats with mutated ATP synthase.
abstract: The BHE/cdb rat has a mutation in adenosine triphosphate (ATP) synthase that impairs insulin secretion. However, male BHE/cdb rats have normal circulating glucose and enhanced glucose tolerance. The aim of the current study was to identify mechanisms of enhanced glucose tolerance. The respiratory exchange ratio was increased, indicating increased oxidation of carbohydrate in BHE/cdb rats, consistent with increases in liver pyruvate dehydrogenase activity and muscle citrate synthase activity. Liver also exhibited diminished phosphoenol pyruvate carboxykinase content, which correlated with a decreased counter-regulatory response in the insulin tolerance test. Signaling via Akt or AMP-dependent kinase pathways in the liver could not account for lower blood glucose. We conclude that chronically low insulin secretion leads to adaption in glucose metabolism primarily in liver to maintain euglycemia.
authors.affiliation: Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Harasym
authors.forename: A Brianne
authors.initials: AB
authors.lastname: Thrush
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Chan
mesh_terms: D025181:ATP Synthetase Complexes / Q000235:genetics* / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats
chemical_list: D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D002950:Citrate (si)-Synthase; D025181:ATP Synthetase Complexes; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose