Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes.
Level 4 - case-series / case-control
Cross-sectional comparative study with human tissue biopsies across small clinical groups.
PubMed 15616005 · doi:10.2337/diabetes.54.1.8
What was done
Percutaneous vastus lateralis muscle biopsies were obtained from 31 volunteers: 11 with type 2 diabetes, 12 age-, sex-, and weight-matched obese sedentary nondiabetic controls, and 8 lean controls. Subsarcolemmal and intermyofibrillar mitochondrial fractions were isolated by differential centrifugation and digestion techniques to measure electron transport chain activity, mitochondrial DNA content, and ultrastructure by transmission electron microscopy.
What was found
Overall electron transport chain activity was similar between type 2 diabetic and obese subjects. Subsarcolemmal mitochondrial electron transport chain activity was significantly lower in type 2 diabetic subjects compared to obese controls (0.017 ± 0.003 vs. 0.034 ± 0.007 units/mU creatine kinase, P = 0.01) and sevenfold lower compared to lean subjects (P < 0.01). Intermyofibrillar electron transport chain activity was similar in diabetic and obese subjects, though lower than in lean subjects. Transmission electron microscopy confirmed the reduction in subsarcolemmal mitochondria. While mtDNA was reduced in both diabetic and obese groups, the decrement in electron transport chain activity was proportionately greater.
Why it matters
This study shows that mitochondrial impairment in type 2 diabetic skeletal muscle is predominantly localized to the subsarcolemmal mitochondrial subpopulation, identifying a specific subcellular deficit that may contribute to muscle insulin resistance.
Limits
The study is limited by a small sample size (n = 31 total across three groups) and a cross-sectional design that cannot establish causality. Functional in vivo substrate oxidation, insulin signaling intermediates, and clinical metabolic outcomes were not reported in the abstract.
Cited by
- supports People with type 2 diabetes have mitochondria that function roughly half as effectively as those in people without type 2 diabetes.