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Postprandial insulin release augments tissue perfusion through a nitric-oxide (NO) dependent mechanism and increases glucose storage. In insulin resistance (IR), abnormalities in NO signaling and the ability to increase skeletal muscle capillary blood volume (CBV) are thought to contribute to hyperglycemia. Whether abnormal capillary function plays a role in the development of IR is unknown. Our aims were to temporally characterize obesity, IR, and muscle CBV response in primates; and to investigate the role of other vasodilators such as epoxyeicosatrienoic acids (EETs).
Ten activity restricted adult rhesus macaques were studied at baseline and every 4-6 mos for 2 yrs after starting a high-fat diet (HFD). At each interval, intravenous glucose tolerance test (IVGTT), X-ray absorptiometry for truncal fat, brachial artery flow-mediated vasodilation (FMD), contrast enhanced ultrasound for baseline and peak skeletal muscle CBV during an IVGTT, and blood collection for EETs were performed.
HFD produced a 20% increase in weight and an 80% increase in truncal fat by 4 mos. Glucose utilization rate (KG) on IVGTT initially decreased at 4 mos, became stable, then fell again at 24 mos to 26% of baseline. Skeletal muscle CBV at rest and after glucose challenge initially increased at 4 months (p<0.05), became stable, and then declined precipitously (p<0.05) at 24 months. With regards to mechanisms, FMD decreased over 2 yrs by 54 % (p=0.06) while plasma EETs increased (p <0.01). There was a strong reciprocal relationship (R2 = 0.8) between NO bioactivity and plasma EETs for 18 mos prior to the precipitous decline in both KG and CBV.
In the development of diet-induced obesity and IR, there is an early compensatory increase in skeletal muscle CBV that eventually falls as IR progresses. Production of EETs may be responsible for the increase in CBV that helps to maintain stability in the degree of IR until there is late failure of tissue perfusion and further IR. These results are important for understanding the regulatory mechanisms that control tissue blood flow and for the development of new therapies for treating IR and diabetes mellitus.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Imaging: Echo – Contrast Echocardiography/Vascular Imaging
Abstract Category: 18. Imaging: Echo
Presentation Number: 1225-327
- 2013 American College of Cardiology Foundation