Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes

Abstract

Aims/hypothesis Mitochondrial respiration has been linked to insulin resistance. We studied mitochondrial respiratory capacity and substrate sensitivity in patients with type 2 diabetes (patients), and obese and lean control participants.

Physically active vs. inactive lifestyle, muscle properties, and glucose homeostasis in middle-aged and older twins

“…One of the suggestions for the association could be the reduced aerobic capacity among the inactive co-twins (Leskinen et al 2010). However, although the number of mitochondria might be reduced in an insulin resistant skeletal muscle, the mitochondrial respiratory capacity can be maintained normal (Larsen et al 2011). …”

Effects of exercise training on mitochondrial function in patients with type 2 diabetes

“…The results from the pilot study (respirometric measurements) are provided in Figures 2-4. The method we used has been described previously [12,16] . No differences were seen in mitochondrial substrate sensitivity for octanoyl carnitine between the groups and both groups increased their sensitivity for octanoyl carnitine in the trained leg (Figure 2A).…”

“…In the past decade mitochondrial dysfunction in skeletal muscle has been linked to insulin resistance [3][4][5][6][7] , but an agreement has not been reached and the majority of data does not support this notion [8][9][10][11][12][13][14][15][16][17] . It has been shown that patients with type 2 diabetes have 30% lower mitochondrial content in their skeletal muscle compared to healthy control subjects [12,18] , and yet the intrinsic mitochondrial function (i.e., respiratory rates normalized for mitochondrial content) is similar in these two groups [12][13][14] .…”

“…One explanation could be that the matching of the subjects is not optimal in the studies [12,18,21] where a lower mitochondrial content was reported. If the healthy control group and the patients with type 2 diabetes are carefully matched for physical activity level and maximal oxygen uptake, no differences exist in mitochondrial content, or intrinsic mitochondrial function [16] . Another question is the likelyhood of a marked decrease in mitochondrial content in the skeletal muscle of patients with type 2 diabetes.…”

Mitochondrial Metabolism and Insulin Action

“…Some studies examining respiration or fatty acid oxidation in isolated mitochondria or permeabilised muscle fibres, have reported that the functional capacity per mitochondrion in insulin resistant and/or type 2 diabetic subjects is similar or only very mildly reduced [85,88,91,[101][102][103] in insulin-resistant individuals, but when normalized to muscle mass, a substantial reduction is seen in insulin-resistant subjects [85,88,101]. These studies therefore only see marked differences when mitochondrial capacity is expressed per unit mass of skeletal muscle and thus indicate that in vivo mitochondrial defects observed with MRS may be more strongly related to reductions in mitochondrial number, than to substantial intrinsic mitochondrial defects.…”