Details

Autor(en) / Beteiligte

• INYARD, April C
• CHONG, Daniel G
• KLIBANOV, Alexander L
• BARRETT, Eugene J

Titel

Muscle Contraction, but Not Insulin, Increases Microvascular Blood Volume in the Presence of Free Fatty Acid–Induced Insulin Resistance

Ist Teil von

• Diabetes (New York, N.Y.), 2009-11, Vol.58 (11), p.2457-2463

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Muscle Contraction, but Not Insulin, Increases Microvascular Blood Volume in the Presence of Free Fatty Acid–Induced Insulin Resistance April C. Inyard , Daniel G. Chong , Alexander L. Klibanov and Eugene J. Barrett From the University of Virginia, Charlottesville, Virginia. Corresponding author: Eugene J. Barrett, ejb8x{at}virginia.edu . Abstract OBJECTIVE Insulin and contraction each increase muscle microvascular blood volume (MBV) and glucose uptake. Inhibiting nitric oxide synthase blocks insulin's but not contraction's effects. We examined whether contraction could augment the MBV increase seen with physiologic hyperinsulinemia and whether free fatty acid (FFA)-induced insulin resistance differentially affects contraction- versus insulin-mediated increases in MBV. RESEARCH DESIGN AND METHODS Rats were fasted overnight. Plasma FFAs were increased by intralipid/heparin infusion (3 h), insulin was increased with a euglycemic clamp (3 mU · min −1 · kg −1 ), and hindlimb muscle contraction was electrically stimulated. Muscle MBV was measured using contrast-enhanced ultrasound. Insulin transport into muscle was measured using 125 I-insulin. BQ-123 (0.4 mg/h) was used to block the endothelin-1 (ET-1) receptor A. RESULTS Superimposing contraction on physiologic hyperinsulinemia increased MBV within 10 min by 37 and 67% for 0.1 or 1 Hz, respectively ( P < 0.01). FFA elevation alone did not affect MBV, whereas 0.1 Hz stimulation doubled MBV ( P < 0.05) and increased muscle insulin uptake ( P < 0.05) despite high FFA. Physiologic hyperinsulinemia during FFA elevation paradoxically decreased MBV ( P < 0.05). This MBV decrease was reversed by either 0.1 Hz contraction or ET-1 receptor A antagonism, and the combination raised MBV above basal. CONCLUSIONS Contraction recruits microvasculature beyond that seen with physiologic hyperinsulinemia by a distinct mechanism that is not blocked by FFA-induced vascular insulin resistance. The paradoxical MBV decline seen with insulin plus FFA may result from differential inhibition of insulin-stimulated nitric oxide–dependent vasodilation relative to ET-1 vasoconstriction. Our results implicate ET-1 as a potential mediator of FFA-induced vascular insulin resistance. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received August 5, 2008. Accepted July 16, 2009. © 2009 American Diabetes Association