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

• Published in: Diabetologia 2021-05, Vol.64 (5), p.1158-1168
• Main Authors: Koh, Han-Chow E., van Vliet, Stephan, Meyer, Gretchen A., Laforest, Richard, Gropler, Robert J., Klein, Samuel, Mittendorfer, Bettina
• Format: Article
• Language: English
• Subjects: Adult; Antidepressants; Biological Transport - drug effects; Biopsy; Diabetes; Fat-free body mass; Female; Fluorodeoxyglucose F18; Glucose; Glucose - metabolism; Glucose - pharmacokinetics; Glucose Clamp Technique; Human Physiology; Humans; Insulin; Insulin - metabolism; Insulin - pharmacology; Insulin resistance; Insulin Resistance - physiology; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Obesity; Obesity - diagnostic imaging; Obesity - metabolism; Obesity - pathology; Perfusion; Positron emission tomography; Quadriceps muscle; Quadriceps Muscle - diagnostic imaging; Quadriceps Muscle - drug effects; Quadriceps Muscle - metabolism; Quadriceps Muscle - pathology; Thinness - diagnostic imaging; Thinness - metabolism; Thinness - pathology
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-021-05383-w

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 [ 2 H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [ 15 O]H 2 O (to assess muscle perfusion) and [ 18 F]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 ( r 2  = 0.65, p