Temporal changes in skeletal muscle capillary responses and endothelial-derived vasodilators in obesity-related insulin resistance

Scott M. Chadderdon, J. Todd Belcik, Lindsay Bader, Dawn M. Peters, Paul Kievit, Nabil J. Alkayed, Sanjiv Kaul, Kevin L. Grove, Jonathan R. Lindner

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The inability of insulin to increase skeletal muscle capillary blood volume (CBV) reduces glucose uptake in insulin resistance (IR). We hypothesized that abnormalities in endothelial-derived vasodilator pathways are temporally associated with the development of IR and an impaired ability to increase skeletal muscle CBV. A comprehensive metabolic and vascular screening assessment was performed on 10 adult rhesus macaques at baseline and every 4-6 months for 2 years after starting a high-fat diet supplemented with fructose. Diet changes resulted in an 80% increase in truncal fat by 4 months. Hyperinsulinemia and decreased glucose utilization were observed from 4 to 18 months. At 24 months, pancreatic secretory function and the glucose utilization rate declined. CBV at rest and during an intravenous glucose tolerance test demonstrated a sustained increase from 4 to 18 months and then abruptly fell at 24 months. Nitric oxide bioavailability progressively decreased over 2 years. Conversely, endothelial-derived vasodilators progressively increased over 18 months and then abruptly decreased at 24 months in concert with the CBV. The increase in basal and glucose-mediated CBV early in IR may represent a compensatory response through endothelial-derived vasodilator pathways. The inability to sustain a vascular compensatory response limits glucose-mediated increases in CBV, which correlates with the severity of IR.

Original languageEnglish (US)
Pages (from-to)2249-2257
Number of pages9
JournalDiabetes
Volume65
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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