Type 2 Diabetes Mellitus and Skeletal Muscle Metabolic Function

Esther Phielix*, Marco Mensink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

66 Citations (Scopus)


Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant state.

Original languageEnglish
Pages (from-to)252-258
Number of pages7
JournalPhysiology and Behavior
Issue number2
Publication statusPublished - 23 May 2008
Externally publishedYes


  • Insulin resistance
  • Mitochondrial function
  • Muscle metabolic function
  • Type 2 diabetes


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