Background: Disturbed Wnt signalling has been implicated in numerous diseases, including type 2 diabetes and the metabolic syndrome. Wnt and insulin signalling pathways exhibit cross-talk at multiple levels. Wnt proteins enhance phosphorylation of insulin signaling molecules in skeletal muscle cells. Sclerostin is a bone-derived circulating inhibitor of the Wnt signalling pathway and is increased in obesity. Obesity is also characterised by defects in insulin signalling in muscle cells resulting in peripheral insulin resistance. It is hitherto not reported whether circulating Wnt signalling inhibitors are related to impaired insulin-induced effects on glucose uptake in lean and/or obese individuals. To examine whether serum sclerostin is associated with insulin-induced whole-body glucose uptake and whether this association differs between obese and lean individuals. Methods: Whole-body glucose uptake (WBGU) was assessed by a hyperinsulinaemic euglycaemic clamp and expressed per lean body mass in lean and obese healthy women (BMI≤25 vs. BMI≥30 kg/cm2). Serum sclerostin was measured using the MesoScale Discovery chemiluminescence assay. Results: Twenty-one lean and 21 obese women were included (mean±SD; age 37±11 years, BMI 22.0±2.0 kg/cm2 and n=21; age 39±12 years; BMI 34.8±4.9 kg/cm2, respectively). Serum sclerostin was higher in obese as compared with lean women (123±33 vs. 93±33 ng/L, p=0.006). Insulin infusion did not affect serum sclerostin. Due to interaction for obesity in the relationship between serum sclerostin and WBGU (p=0.014), further analyses were stratified for obesity. In obese but not lean women serum sclerostin was related to WBGU (-0.089±0.028 mg•kg−1•min−1, p=0.005) after adjustment for age. Further adjustment for BMI attenuated the association (-0.067±0.028 mg•kg−1•min−1, p=0.026). This relationship was not confounded by renal function, blood pressure or lipid levels. Conclusion: Serum sclerostin is inversely related to insulininduced whole-body glucose uptake in obese but not lean women. Further studies after direct effects of sclerostin on insulin action are warranted. Disclosure: The authors declared no competing interests.
de Jongh, R., Serne, E., Meijer, R., & den Heijer, M. (2015). Serum sclerostin is associated with impaired insulin-induced whole-body glucose uptake in obesity. The 4th Joint Meeting of ECTS and IBMS.