Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs

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Christopher, Michael J, Rantzau, Christian, McConell, Glenn ORCID: 0000-0002-8572-9065, Kemp, Bruce E and Alford, Frank P (2005) Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs. Journal of Applied Physiology, 98 (3). pp. 930-939. ISSN 8750-7587


The separate impacts of the chronic diabetic state and the prevailing hyperglycemia on plasma substrates and hormones, in vivo glucose turnover, and ex vivo skeletal muscle (SkM) during exercise were examined in the same six dogs before alloxan-induced diabetes (prealloxan) and after 4–5 wk of poorly controlled hyperglycemic diabetes (HGD) in the absence and presence of ∼300-min phlorizin-induced (glycosuria mediated) normoglycemia (NGD). For each treatment state, the ∼15-h-fasted dog underwent a primed continuous 150-min infusion of [3-3H]glucose, followed by a 30-min treadmill exercise test (∼65% maximal oxygen capacity), with SkM biopsies taken from the thigh (vastus lateralis) before and after exercise. In the HGD and NGD states, preexercise hepatic glucose production rose by 130 and 160%, and the metabolic clearance rate of glucose (MCRg) fell by 70 and 37%, respectively, compared with the corresponding prealloxan state, but the rates of glucose uptake into peripheral tissues (Rdtissue) and total glycolysis (GF) were unchanged, despite an increased availability of plasma free fatty acid in the NGD state. Exercise-induced increments in hepatic glucose production, Rdtissue, and plasma-derived GF were severely blunted by ∼30–50% in the NGD state, but increments in MCRg remained markedly reduced by ∼70–75% in both diabetic states. SkM intracellular glucose concentrations were significantly elevated only in the HGD state. Although Rdtissue during exercise in the diabetic states correlated positively with preexercise plasma glucose and insulin and GF and negatively with preexercise plasma free fatty acid, stepwise regression analysis revealed that an individual's preexercise glucose and GF accounted for 88% of Rdtissue during exercise. In conclusion, the prevailing hyperglycemia in poorly controlled diabetes is critical in maintaining a sufficient supply of plasma glucose for SkM glucose uptake during exercise. During phlorizin-induced NGD, increments in both Rdtissue and GF are impaired due to a diminished fuel supply from plasma glucose and a sustained reduction in increments of MCRg.

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Online ISSN: 1522-1601

Item type Article
DOI 10.1152/japplphysiol.00687.2004
Official URL
Subjects Historical > FOR Classification > 1102 Cardiorespiratory Medicine and Haematology
Historical > FOR Classification > 1106 Human Movement and Sports Science
Historical > Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Keywords ResPubID22173. hyperglycemia, glucose uptake, plasma-derived glycolysis, skeletal muscle, free fatty acids, metabolic clearance rate of glucose, phlorizin-induced normoglycemia, alloxan-diabetic dogs
Citations in Scopus 9 - View on Scopus
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