title: Globular adiponectin enhances muscle insulin action via microvascular recruitment and increased insulin delivery.
abstract: BACKGROUND
  Adiponectin enhances insulin action and induces nitric oxide-dependent vasodilatation. Insulin delivery to muscle microcirculation and transendothelial transport are 2 discrete steps that limit insulin's action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action.
  
  
  OBJECTIVE
  To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo.
  
  
  RESULTS
  Overnight fasted adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment, using contrast-enhanced ultrasound, on insulin-mediated microvascular recruitment and whole-body glucose disposal, using contrast-enhanced ultrasound and insulin clamp, and on muscle insulin clearance and uptake with (125)I-insulin. Globular adiponectin potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ≈30% to 40% increase in muscle insulin uptake and clearance, and ≈30% increase in insulin-stimulated whole-body glucose disposal. Inhibition of endothelial nitric oxide synthase abolished globular adiponectin-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, globular adiponectin dose-dependently increased endothelial nitric oxide synthase phosphorylation but had no effect on endothelial cell internalization of insulin.
  
  
  CONCLUSIONS
  Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action.
authors: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors: Lina
authors: L
authors: Zhao
authors: Weidong
authors: W
authors: Chai
authors: Zhuo
authors: Z
authors: Fu
authors: Zhenhua
authors: Z
authors: Dong
authors: Kevin W
authors: KW
authors: Aylor
authors: Eugene J
authors: EJ
authors: Barrett
authors: Wenhong
authors: W
authors: Cao
authors: Zhenqi
authors: Z
authors: Liu
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting / Q000097:blood; D015309:Glucose Clamp Technique; D006614:Hindlimb; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000378:metabolism; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D055806:Microvessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat