Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes

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Abstract

Aim: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM. Patients and Methods: Eleven patients with T2DM [9 males, 2 females; age, 52.8 ± 2.5 yr (mean ± se); body mass index, 30.2 ± 1.1 kg/m 2] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 ± 2.7 yr; body mass index, 30.6 ± 1.1 kg/m2) were included as controls. Results: Hemoglobin A1c (9.1 ± 0.5 to 7.5 ± 0.3%; P < 0.001) and fasting plasma glucose (12.7 ± 1.1 to 6.5 ± 0.3 mmol/liter; P < 0.001) were reduced aftertreatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I + II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r2 = 0.53; P < 0.05) but not after treatment [r2 = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM. Discussion: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated. Copyright © 2009 by The Endocrine Society.

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Rabøl, R., Højberg, P. M. V., Almdal, T., Boushel, R., Haugaard, S. B., Madsbad, S., & Dela, F. (2009). Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 94(4), 1372–1378. https://doi.org/10.1210/jc.2008-1475

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