NDLI: Obesity, type 2 diabetes, and impaired insulin stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.

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Obesity, type 2 diabetes, and impaired insulin stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.

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Obesity, type 2 diabetes, and impaired insulin stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Reynolds, Leryn J. Credeur, Daniel P. Manrique, Camila Padilla, Jaume Fadel, Paul J. Thyfault, John P.
Description	Author Affiliation: Reynolds LJ ( University of Kentucky.); Credeur DP ( University of Southern Mississippi.); Manrique C ( University of Missouri.); Padilla J ( University of Missouri.); Fadel PJ ( University of Texas at Arlington.); Thyfault JP ( University of Kansas Medical Center jthyfault@kumc.edu.)
Abstract	Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D (glucose disposal rate (GDR): 6.6±1.6 mg/kg LBM/min) and eleven lean insulin sensitive subjects (Lean GDR: 12.9±1.2 mg/kg LBM/min), underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in eleven medication- naïve, obese, non-T2D subjects. ET-1, peNOS (ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7±6.5% baseline, T2D: +20.8±5.2% baseline, p<0.05). peNOS/eNOS content was higher in Lean under basal conditions and although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D (p<0.05). ET-1 mRNA and peptide were 2.25±0.50 and 1.52±0.11 fold higher in obese T2D compared to Lean at baseline, and ET-1 peptide remained 2.02±1.9 fold elevated in obese T2D after insulin infusion (p<0.05), but did not increase with insulin in either group (p>0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 (p=0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients.
File Format	HTM / HTML
ISSN	87507587
e-ISSN	15221601
Journal	Journal of Applied Physiology
Language	English
Publisher	American Physiological Society
Publisher Date	2016-10-27
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Applied Physiology Molecular Biology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Sports Science

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