Obesity blunts microvascular recruitment in human forearm muscle after a mixed meal

Michelle A Keske, Lucy H Clerk, Wendie J Price, Linda A Jahn, Eugene J Barrett, Michelle A Keske, Lucy H Clerk, Wendie J Price, Linda A Jahn, Eugene J Barrett

Abstract

Objective: Ingestion of a mixed meal recruits flow to muscle capillaries and increases total forearm blood flow in healthy young lean people. We examined whether these vascular responses are blunted by obesity.

Research design and methods: We fed eight middle-aged lean and eight obese overnight-fasted volunteers a liquid mixed meal (480 kcal). Plasma glucose and insulin were measured every 30 min, and brachial artery flow and muscle microvascular recruitment (contrast ultrasound) were assessed every 60 min over 2 h after the meal.

Results: By 30 min, plasma glucose rose in both the lean (5.1 +/- 0.1 vs. 6.7 +/- 0.4 mmol/l, P < 0.05) and the obese groups (5.4 +/- 0.2 vs. 6.7 +/- 0.4 mmol/l, P < 0.05). Plasma insulin rose (28 +/- 4 vs. 241 +/- 30 pmol/l, P < 0.05) by 30 min in the lean group and remained elevated for 2 h. The obese group had higher fasting plasma insulin levels (65 +/- 8 pmol/l, P < 0.001) and a greater postmeal area under the insulin-time curve (P < 0.05). Brachial artery flow was increased at 120 min after the meal in the lean group (38 +/- 6 vs. 83 +/- 16 ml/min, P < 0.05) but not in the obese group. Muscle microvascular blood volume rose by 120 min in the lean group (14.4 +/- 2.2 vs. 24.4 +/- 4.2 units, P < 0.05) but not in the obese group.

Conclusions: A mixed meal recruits muscle microvasculature in lean subjects, and this effect is blunted by obesity. This impaired vascular recruitment lessens the endothelial surface available and may thereby impair postprandial glucose disposal.

Figures

Figure 1
Figure 1
Time courses of plasma glucose and insulin concentrations after the ingestion of a mixed meal in lean (○, n = 8) and obese (●, n = 8) volunteers. Measurements were made every 30 min for 2 h. Data are means ± SEM. *P < 0.05 vs. 0 min; †P < 0.05 vs. lean; two-way repeated-measures ANOVA and post hoc Student-Newman-Keuls test. ‡P < 0.001 vs. lean; Student's unpaired t test.
Figure 2
Figure 2
Time courses of brachial artery diameter, brachial artery flow velocity, and total brachial artery blood flow measured by Doppler ultrasound after the ingestion of a mixed meal in lean (□, n = 8) and obese (■, n = 8) volunteers. Data are means ± SEM. *P < 0.05 vs. 0 min; †P < 0.05 vs. lean; #P = 0.055 vs. lean; two-way repeated-measures ANOVA and post hoc Student-Newman-Keuls test.
Figure 3
Figure 3
Time course of forearm MBV, MFV, and MBV × MFV measured by contrast-enhanced ultrasound after the ingestion of a mixed meal in lean (□, n = 8) and obese (■, n = 8) volunteers. Data are means ± SEM. *P < 0.05 vs. 0 min; #P = 0.065 vs. 0 min; repeated-measures ANOVA on ranks and post hoc Student-Newman-Keuls test.

References

    1. DeFronzo RA, Ferrannini E, Sato Y, Felig P, Wahren J. Synergistic interaction between exercise and insulin on peripheral glucose uptake. J Clin Invest 1981; 68: 1468– 1474
    1. Baron AD. Hemodynamic actions of insulin. Am J Physiol 1994; 267: E187– E202
    1. Rattigan S, Clark MG, Barrett EJ. Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment. Diabetes 1997; 46: 1381– 1388
    1. Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes 2006; 55: 1436– 1442
    1. Vincent MA, Dawson D, Clark AD, Lindner JR, Rattigan S, Clark MG, Barrett EJ. Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow. Diabetes 2002; 51: 42– 48
    1. Montagnani M, Chen H, Barr VA, Quon MJ. Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser1179. J Biol Chem 2001; 276: 30392– 30398
    1. Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, Panza JA. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 1999; 100: 820– 825
    1. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man: a novel mechanism for insulin resistance. J Clin Invest 1990; 85: 1844– 1852
    1. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent: a novel action of insulin to increase nitric oxide release. J Clin Invest 1994; 94: 1172– 1179
    1. Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. Methodological aspects, dose-response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects. Diabetologia 1995; 38: 555– 564
    1. Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Invest 1994; 94: 2511– 2515
    1. Vincent MA, Clerk LH, Lindner JR, Klibanov AL, Clark MG, Rattigan S, Barrett EJ. Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes 2004; 53: 1418– 1423
    1. Dawson D, Vincent MA, Barrett EJ, Kaul S, Clark A, Leong-Poi H, Lindner JR. Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound. Am J Physiol Endocrinol Metab 2002; 282: E714– E720
    1. Renkin EM, Renkin EM, Michel CC, Geiger SR. Control of microcirculation and blood-tissue exchange. In Handbook of Physiology. Section 2: The Cardiovascular System Vol. IV Renkin E., Michel CC. Eds. Bethesda, MD, American Physiological Society, 1984, p. 627– 687
    1. Coggins M, Lindner J, Rattigan S, Jahn L, Fasy E, Kaul S, Barrett E. Physiologic hyperinsulinemia enhances human skeletal muscle perfusion by capillary recruitment. Diabetes 2001; 50: 2682– 2690
    1. Hoost U, Kelbaek H, Rasmusen H, Court P, Christensen NJ, Pedersen-Bjergaard U, Lorenzen T. Haemodynamic effects of eating: the role of meal composition. Clin Sci 1996; 90: 269– 276
    1. Baron AD, Laakso M, Brechtel G, Hoit B, Watt C, Edelman SV. Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity. J Clin Endocrinol Metab 1990; 70: 1525– 1533
    1. Hernandez MA, Jensen MD. Contribution of blood flow to leg glucose uptake during a mixed meal. Diabetes 1995; 44: 1165– 1169
    1. Vincent MA, Clerk LH, Lindner JR, Price WJ, Jahn LA, Leong-Poi H, Barrett EJ. Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab 2006; 290: E1191– E1197
    1. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 1998; 97: 473– 483
    1. Quon MJ. QUICKI is a useful and accurate index of insulin sensitivity. J Clin Endocrinol Metab 2002; 87: 949– 951
    1. Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 2005; 112: 179– 184
    1. Chiu JD, Richey JM, Harrison LN, Zuniga E, Kolka CM, Kirkman E, Ellmerer M, Bergman RN. Direct administration of insulin into skeletal muscle reveals that the transport of insulin across the capillary endothelium limits the time course of insulin to activate glucose disposal. Diabetes 2008; 57: 828– 835
    1. Richey JM, Ader M, Moore D, Bergman RN. Angiotensin II induces insulin resistance independent of changes in interstitial insulin. Am J Physiol 1999; 277: E920– E926
    1. Park J, Lemieux S, Lewis GF, Kuksis A, Steiner G. Chronic exogenous insulin and chronic carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats. J Lipid Res 1997; 38: 2529– 2536

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