title: Plasma 25-Hydroxyvitamin D Is Related to Protein Signaling Involved in Glucose Homeostasis in a Tissue-Specific Manner.
abstract: Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r= 0.19,p= 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21and βSer9in skeletal muscle (r= -0.66,p= 0.015 andr= -0.53,p= 0.06, respectively) and higher GSK-3 αSer21and βSer9phosphorylation in adipose tissue (r= 0.82,p< 0.01 andr= 0.62,p= 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r= 0.78,p< 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r= 0.71,p= 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissue.
authors.affiliation: Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne VIC 8001, Australia. lewan.parker@live.vu.edu.au.
authors.forename: Lewan
authors.initials: L
authors.lastname: Parker
authors.affiliation: Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne VIC 8001, Australia. Itamar.Levinger@vu.edu.au.
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, MHRP, 43-51 Kanooka Grove, Clayton VIC 3168, Australia. aya.mousa@monash.edu.
authors.forename: Aya
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Waurn Ponds VIC 3217, Australia. kirsten.howlett@deakin.edu.au.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Howlett
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, MHRP, 43-51 Kanooka Grove, Clayton VIC 3168, Australia. barbora.decourten@monash.edu.|Diabetes and Vascular Medicine Unit, Monash Health, Locked Bag 29, Clayton VIC 3168, Australia. barbora.decourten@monash.edu.
authors.forename: Barbora
authors.initials: B
authors.lastname: de Courten
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009928:Organ Specificity; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: 25-hydroxyvitamin D; diabetes; glucose homeostasis; insulin resistance; insulin signaling; vitamin D