TY - JOUR
T1 - Genetic and metabolic effects on skeletal muscle AMPK in young and older twins
AU - Mortensen, Brynjulf
AU - Poulsen, Pernille
AU - Wegner, Lise
AU - Stender-Petersen, Kirstine Lynge
AU - Ribel-Madsen, Rasmus
AU - Friedrichsen, Martin
AU - Birk, Jesper Bratz
AU - Vaag, Allan
AU - Wojtaszewski, Jørgen
N1 - CURIS 2009 5200 105
PY - 2009
Y1 - 2009
N2 - The protein complex AMP-activated protein kinase (AMPK) is believed to play an important role in the regulation of skeletal muscle glucose and lipid metabolism. Defects in the AMPK system might therefore be an important factor in the pathogenesis of type 2 diabetes. We aimed to identify genetic and environmental mechanisms involved in the regulation of AMPK expression and activity and to examine the association between AMPK protein levels and activity on one hand, and glucose and fat metabolism on the other hand. We investigated skeletal muscle biopsies from 100 young and 82 older mono- and dizygotic non-diabetic twins excised during the basal and insulin-stimulated states of a physiological hyperinsulinemic-euglycemic clamp. AMPK subunit alpha1, alpha2, and gamma3 mRNA expression was investigated using real-time PCR and Western blotting was employed to measure protein levels. Multiple regression analyses indicated that skeletal muscle AMPK mRNA and protein expression as well as activity were regulated by sex, age, obesity, and aerobic capacity. Comparison of intraclass correlations on AMPK measures from mono- and dizygotic twins suggested that skeletal muscle AMPK expression was under minor genetic influence. AMPK gamma3 protein expression and activity were negatively related to whole-body glucose uptake through the non-oxidative metabolic pathway, and positively related to phosphorylation of glycogen synthase. In conclusion, our results suggest that skeletal muscle AMPK expression is under minor genetic control but regulated by age and sex and associated with obesity and aerobic capacity. Furthermore, our results indicate a role for gamma3-containing AMPK complexes in down-regulation of insulin-stimulated non-oxidative glucose metabolism possibly through inhibition of glycogen synthase activity. Key words: AMP-activated protein kinase, heritability, glucose metabolism.
AB - The protein complex AMP-activated protein kinase (AMPK) is believed to play an important role in the regulation of skeletal muscle glucose and lipid metabolism. Defects in the AMPK system might therefore be an important factor in the pathogenesis of type 2 diabetes. We aimed to identify genetic and environmental mechanisms involved in the regulation of AMPK expression and activity and to examine the association between AMPK protein levels and activity on one hand, and glucose and fat metabolism on the other hand. We investigated skeletal muscle biopsies from 100 young and 82 older mono- and dizygotic non-diabetic twins excised during the basal and insulin-stimulated states of a physiological hyperinsulinemic-euglycemic clamp. AMPK subunit alpha1, alpha2, and gamma3 mRNA expression was investigated using real-time PCR and Western blotting was employed to measure protein levels. Multiple regression analyses indicated that skeletal muscle AMPK mRNA and protein expression as well as activity were regulated by sex, age, obesity, and aerobic capacity. Comparison of intraclass correlations on AMPK measures from mono- and dizygotic twins suggested that skeletal muscle AMPK expression was under minor genetic influence. AMPK gamma3 protein expression and activity were negatively related to whole-body glucose uptake through the non-oxidative metabolic pathway, and positively related to phosphorylation of glycogen synthase. In conclusion, our results suggest that skeletal muscle AMPK expression is under minor genetic control but regulated by age and sex and associated with obesity and aerobic capacity. Furthermore, our results indicate a role for gamma3-containing AMPK complexes in down-regulation of insulin-stimulated non-oxidative glucose metabolism possibly through inhibition of glycogen synthase activity. Key words: AMP-activated protein kinase, heritability, glucose metabolism.
U2 - 10.1152/ajpendo.00058.2009
DO - 10.1152/ajpendo.00058.2009
M3 - Journal article
C2 - 19671840
SN - 0193-1849
VL - 297
SP - E956-E964
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 4
ER -
