Rabol 2009 Diabetes Obes Metab

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Rabol R, Hojberg PM, Almdal T, Boushel RC, Haugaard SB, Madsbad S, Dela F (2009) Improved glycaemic control decreases inner mitochondrial membrane leak in type 2 diabetes. Diabetes Obes Metab 11:355-60.

» PMID:19267714

Rabol R, Hojberg PM, Almdal T, Boushel RC, Haugaard SB, Madsbad S, Dela F (2009) Diabetes Obes Metab

Abstract: AIM: Several mechanisms have been targeted as culprits of weight gain during antihyperglycaemic treatment in type 2 diabetes (T2DM). These include reductions in glucosuria, increased food intake from fear of hypoglycaemia, the anabolic effect of insulin, decreased metabolic rate and increased efficiency in fuel usage. The purpose of the study was to test the hypothesis that mitochondrial efficiency increases as a result of insulin treatment in patients with type 2 diabetes.

METHODS: We included ten patients with T2DM (eight males) on oral antidiabetic treatment, median age: 51.5 years (range: 39-67) and body mass index (BMI): 30.1 +/- 1.2 kg/m2 (mean +/- s.e.). Muscle biopsies from m. vastus lateralis and m. deltoideus were obtained before and after seven weeks of intensive insulin treatment, and mitochondrial respiration was measured using high-resolution respirometry. State 3 respiration was measured with the substrates malate, pyruvate, glutamate, succinate and ADP. State 4o was measured with addition of oligomycine. An age, sex and BMI-matched control group was also included.

RESULTS: HbA1c improved significantly and the patients gained on average 3.4 +/- 0.9 kg. Before treatment, respiratory control ratios (RCRs) of the T2DM were lower than the obese controls [2.6 vs. 3.2 (p < 0.05)], but RCR returned to the levels of the control subjects during treatment. Average state 4o of arm and leg declined by 14% (p < 0.05) during insulin treatment.

CONCLUSIONS: Tight glycaemic control leads to reductions in inner mitochondrial membrane leak and increased efficiency of mitochondria. This change in mitochondrial physiology could contribute to the weight gain seen with antihyperglycaemic treatment.

Keywords: Diabetes mellitus, Diabetes treatment, Metabolism, Skeletal muscle metabolism

O2k-Network Lab: DK Copenhagen Dela F, SE Stockholm Boushel RC, CA Vancouver Boushel RC, DK Copenhagen Larsen S

Labels: Pathology: Diabetes  Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

HRR: Oxygraph-2k