Raboel 2009 J Clin Endocrinol Metabol

Rabol R, Hojberg PMV, Almdal T, Boushel RC, Haugaard SB, Madsbad S, Dela F (2009) Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes. J Clin Endocrinol Metabol 94: 1372-1378.

» PMID: 19141588

Rabol R, Hojberg PMV, Almdal T, Boushel RC, Haugaard SB, Madsbad S, Dela F (2009) J Clin Endocrinol Metabol

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/m² ] 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 after treatment. 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.

• O2k-Network Lab: DK_Copenhagen_Dela F, DK_Copenhagen_Boushel RC

Labels: Pathology: Diabetes 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Intact Organism"Intact Organism" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property., Permeabilized tissue  Enzyme: Complex I  Regulation: Ion Homeostasis"Ion Homeostasis" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Substrate; Glucose; TCA Cycle"Substrate; Glucose; TCA Cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 

HRR: Oxygraph-2k