TY - JOUR
T1 - Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity
AU - Koh, Han Chow E.
AU - van Vliet, Stephan
AU - Meyer, Gretchen A.
AU - Laforest, Richard
AU - Gropler, Robert J.
AU - Klein, Samuel
AU - Mittendorfer, Bettina
N1 - Funding Information:
The authors thank the staff of the Center for Human Nutrition, the Clinical Translational Research Unit, the Clinical Translational Imaging Unit and the Division of Radiological Sciences for help with participant recruitment, scheduling and testing and for technical assistance with sample processing and data analysis, and the study participants for their time and effort. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
PY - 2021/5
Y1 - 2021/5
N2 - 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. Graphical abstract: [Figure not available: see fulltext.]
AB - 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. Graphical abstract: [Figure not available: see fulltext.]
KW - Glucose disposal
KW - Glucose uptake
KW - Insulin resistance
KW - Perfusion
UR - http://www.scopus.com/inward/record.url?scp=85099850124&partnerID=8YFLogxK
U2 - 10.1007/s00125-021-05383-w
DO - 10.1007/s00125-021-05383-w
M3 - Article
C2 - 33511440
AN - SCOPUS:85099850124
SN - 0012-186X
VL - 64
SP - 1158
EP - 1168
JO - Diabetologia
JF - Diabetologia
IS - 5
ER -