Insulin-stimulated whole-body (WB) glucose disposal (GD) is thought to occur predominately in skeletal muscle (SM). Studies in animals suggest adipose tissue (AT) could also be an important site of GD, especially in people with obesity and insulin resistance. The interrelationship between adiposity, insulin sensitivity, and organ-specific insulin-stimulated GD is not known. We evaluated WB, SM, and AT insulin-stimulated GD by using the hyperinsulinemic-euglycemic clamp procedure together with [6,6-2H2]glucose infusion and 18F-deoxyglucose positron emission tomography in healthy lean people (n=13, age: 39±12 yrs, BMI: 23±2 kg/m2; body fat: 31±7%, mean±SD) and 27 people with obesity, who were then characterized as insulin sensitive (OIS, n=9, age: 48±10 yrs, body fat: 45±10%) or insulin resistant (OIR, n=9, age: 40±10 yrs, body fat: 48±4%) based on the top and bottom tertile values for WB insulin-stimulated GD. WB insulin-stimulated GD was 60% lower in the OIR (1,636±283 µmol/min) than both the OIS and Lean groups (P<0.01), without a difference between the OIS and Lean groups (4,188±758 and 3,855±1115 µmol/min). Total GD in subcutaneous AT was lower in the OIR than the OIS group (392±134 vs. 663±224 µmol/min) and greater in the OIS than the Lean (305±97 µmol/min, P<0.01) group. However, the contribution of AT to WB GD was greater in the OIR than the OIS and Lean groups (24±6%, 16±5%, and 9±4% of WB GD, P<0.01). GD rate in four major muscle groups (erector spinae, obliques, hamstrings, quadriceps) was 75% lower in the OIR (median [IQR]: 29 [23-35] µmol/kg muscle/min) than the OIS and the Lean groups (P<0.01), without a difference between the OIS and Lean groups (115 [89-139] and 102 [90-127] µmol/kg muscle/min). We conclude that: 1) a decrease in insulin-stimulated SM GD is responsible for the decrease in WB insulin-stimulated GD in the OIR group and 2) AT is a more important site of insulin-stimulated GD in people with obesity, particularly those with insulin resistance, than lean people.
H. Koh: None. S. van Vliet: None. R. Laforest: None. R. Gropler: None. S. Klein: Advisory Panel; Self; Danone Nutricia, Merck & Co., Inc. Research Support; Self; Johnson & Johnson, Pfizer Inc. Stock/Shareholder; Self; Aspire Bariatrics. B. Mittendorfer: None.
American Diabetes Association (1-18-ICTS-119 to B.M.); National Institutes of Health (DK115400, DK56341, DK020579, UL1TR000448)