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- Title
Temporal Changes in Skeletal Muscle Capillary Responses and Endothelial-Derived Vasodilators in Obesity-Related Insulin Resistance.
- Authors
Chadderdon, Scott M.; Belcik, J. Todd; Bader, Lindsay; Peters, Dawn M.; Kievit, Paul; Alkayed, Nabil J.; Kaul, Sanjiv; Grove, Kevin L.; Lindner, Jonathan R.
- 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.
- Subjects
INSULIN resistance; SKELETAL muscle; GLUCOSE; ENDOTHELIAL cells; VASODILATORS; GLUCOSE metabolism; ANIMAL experimentation; DIET; FRUCTOSE; GLUCOSE tolerance tests; HYPERINSULINISM; NITRIC oxide; OBESITY; PANCREAS; PRIMATES; RESEARCH funding; VASOCONSTRICTORS; EICOSANOIDS; PHARMACODYNAMICS
- Publication
Diabetes, 2016, Vol 65, Issue 8, p2249
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db15-1574