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Effects of raising muscle glycogen synthesis rate on skeletal muscle ATP turnover rate in type 2 diabetes

Lookup NU author(s): Dr Ee Lim, Dr Kieren Hollingsworth, Dr Fiona Smith, Professor Peter Thelwall, Professor Roy Taylor

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Abstract

Lim EL, Hollingsworth KG, Smith FE, Thelwall PE, Taylor R. Effects of raising muscle glycogen synthesis rate on skeletal muscle ATP turnover rate in type 2 diabetes. Am J Physiol Endocrinol Metab 301: E1155-E1162, 2011. First published September 13, 2011; doi: 10.1152/ajpendo.00278.2011.-Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. We hypothesized that any impairment in insulin-stimulated muscle ATP production could merely reflect the lower rates of muscle glucose uptake and glycogen synthesis, rather than cause it. If this is correct, muscle ATP turnover rates in type 2 diabetes could be increased if glycogen synthesis rates were normalized by the mass-action effect of hyperglycemia. Isoglycemic- and hyperglycemic-hyperinsulinemic clamps were performed on type 2 diabetic subjects and matched controls, with muscle ATP turnover and glycogen synthesis rates measured using P-31- and C-13-magnetic resonance spectroscopy, respectively. In diabetic subjects, hyperglycemia increased muscle glycogen synthesis rates to the level observed in controls at isoglycemia [from 19 +/- 9 to 41 +/- 12 mu mol.l(-1).min(-1) (P = 0.012) vs. 40 +/- 7 mu mol.l(-1).min(-1) in controls]. This was accompanied by a modest increase in muscle ATP turnover rates (7.1 +/- 0.5 vs. 8.6 +/- 0.7 mu mol.l(-1).min(-1), P = 0.04). In controls, hyperglycemia brought about a 2.5-fold increase in glycogen synthesis rates (100 +/- 24 vs. 40 +/- 7 mu mol.l(-1).min(-1), P = 0.028) and a 23% increase in ATP turnover rates (8.1 +/- 0.9 vs. 10.0 +/- 0.9 mu mol.l(-1).min(-1), P = 0.025) from basal state. Muscle ATP turnover rates correlated positively with glycogen synthesis rates (r(s) = 0.46, P = 0.005). Changing the rate of muscle glucose metabolism in type 2 diabetic subjects alters demand for ATP synthesis at rest. In type 2 diabetes, skeletal muscle ATP turnover rates reflect the rate of glucose uptake and glycogen synthesis, rather than any primary mitochondrial defect.

Publication metadata

Author(s): Lim EL, Hollingsworth KG, Smith FE, Thelwall PE, Taylor R

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Endocrinology and Metabolism

Year: 2011

Volume: 301

Issue: 6

Print publication date: 01/12/2011

ISSN (print): 0193-1849

ISSN (electronic): 1522-1555

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajpendo.00278.2011

DOI: 10.1152/ajpendo.00278.2011

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