Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity

Abstract

Aims/hypothesis: It has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity.

Methods: We measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major muscle groups (erector spinae, obliques, rectus abdominis, hamstrings, quadriceps) in 15 healthy lean people and 37 people with obesity by using the hyperinsulinaemic-euglycaemic clamp procedure in conjunction with [²H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [¹⁵O]H₂O (to assess muscle perfusion) and [¹⁸F]fluorodeoxyglucose (to assess muscle glucose uptake). A biopsy from the vastus lateralis was obtained to assess fibre type composition.

Results: We found: (1) a twofold difference in glucose uptake rates among muscles in both the lean and obese groups (rectus abdominis: 67 [51, 78] and 32 [21, 55] μmol kg^-1 min^-1 in the lean and obese groups, respectively; erector spinae: 134 [103, 160] and 66 [24, 129] μmol kg^-1 min^-1, respectively; median [IQR]) that was unrelated to perfusion or fibre type composition (assessed in the vastus only); (2) the impairment in insulin action in the obese compared with the lean group was not different among muscle groups; and (3) insulin-stimulated whole-body glucose disposal expressed per kg fat-free mass was linearly related with muscle glucose uptake rate (r² = 0.65, p < 0.05).

Conclusions/interpretation: Obesity-associated insulin resistance is generalised across all major muscles, and is not caused by alterations in muscle fibre type composition or perfusion. In addition, insulin-stimulated whole-body glucose disposal relative to fat-free mass provides a reliable index of muscle glucose uptake rate.

Keywords: Glucose disposal; Glucose uptake; Insulin resistance; Perfusion.

Figure 1.

Insulin-stimulated muscle perfusion (a, b) and glucose uptake (c, d) rates in major muscle groups of the torso and thigh in healthy lean people (n=15, left panels, white bars and symbols) and people with obesity (n=37, right panels, orange bars and symbols). Values are median and interquartile range. * significantly different from erector spinae, hamstrings and quadriceps, p<0.05; ^† significantly different from erector spinae, p<0.05; ^‡ significantly different from erector spinae and hamstrings, p<0.05;^§ significantly different from corresponding values in lean people, p<0.05.

Figure 2.

Relationship between insulin-stimulated glucose uptake rates in the erector spinae and obliques in healthy lean people (open circles; n=15) and people with obesity (orange filled circles; n=37).

Figure 3.

Relationships between insulin-stimulated total muscle glucose uptake (product of muscle mass and average glucose uptake rate in the erector spinae, obliques, rectus abdominis, hamstrings, and quadriceps) and whole-body glucose disposal rate (a), and between the composite average insulin-stimulated glucose uptake rate in the five muscle groups and whole-body glucose disposal rate in relation to body weight (b), and fat-free mass (c) in healthy lean people (open circles; n=15) and people with obesity (orange filled circles; n=37). Dashed lines represent the lines of identity.