title: Exercise ameliorates insulin resistance via Ca2+ signals distinct from those of insulin for GLUT4 translocation in skeletal muscles.
abstract: Muscle contraction and insulin induce glucose uptake in skeletal muscle through GLUT4 membrane translocation. Beneficial effects of exercise on glucose homeostasis in insulin-resistant individuals are known to be due to their distinct mechanism between contraction and insulin action on glucose uptake in skeletal muscle. However, the underlying mechanisms are not clear. Here we show that in skeletal muscle, distinct Ca(2+) second messengers regulate GLUT4 translocation by contraction and insulin treatment; d-myo-inositol 1,4,5-trisphosphate/nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose/NAADP are main players for insulin- and contraction-induced glucose uptake, respectively. Different patterns of phosphorylation of AMPK and Ca(2+)/calmodulin-dependent protein kinase II were shown in electrical stimuli (ES)- and insulin-induced glucose uptake pathways. ES-induced Ca(2+) signals and glucose uptake are dependent on glycolysis, which influences formation of NAD(P)-derived signaling messengers, whereas insulin-induced signals are not. High-fat diet (HFD) induced a defect in only insulin-mediated, but not ES-mediated, Ca(2+) signaling for glucose uptake, which is related to a specifically lower NAADP formation. Exercise decreases blood glucose levels in HFD-induced insulin resistance mice via NAADP formation. Thus we conclude that different usage of Ca(2+) signaling in contraction/insulin-stimulated glucose uptake in skeletal muscle may account for the mechanism by which exercise ameliorates glucose homeostasis in individuals with type 2 diabetes.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Korea National Creative Research Laboratory for Ca Signaling Network, Chonbuk National University, Jeonju, Korea.
authors.forename: Dae-Ryoung
authors.initials: DR
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Korea National Creative Research Laboratory for Ca Signaling Network, Chonbuk National University, Jeonju, Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Korea National Creative Research Laboratory for Ca Signaling Network, Chonbuk National University, Jeonju, Korea.
authors.forename: Byung-Ju
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Physical Education, Chonbuk National University, Jeonju, Korea.
authors.forename: Chung-Su
authors.initials: CS
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Korea National Creative Research Laboratory for Ca Signaling Network, Chonbuk National University, Jeonju, Korea Institute of Cardiovascular Research, Chonbuk National University, Jeonju, Korea uhkim@chonbuk.ac.kr.
authors.forename: Uh-Hyun
authors.initials: UH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D005947:Glucose; D002118:Calcium