Skeletal muscle microvascular insulin resistance in type 2 diabetes is not improved by eight weeks of regular walking

Abstract

<jats:p> We aimed to examine if individuals with type 2 diabetes (T2D) exhibit suppressed leg vascular conductance and skeletal muscle capillary perfusion in response to a hyperinsulinemic-euglycemic clamp, and to test whether these two variables are positively correlated. Subsequently, we examined if T2D-associated skeletal muscle microvascular insulin resistance, as well as overall vascular dysfunction, would be ameliorated by an eight-week walking intervention (45 minutes at 60% of heart rate reserve, 5 sessions/week). We report that, relative to healthy subjects, overweight and obese individuals with T2D exhibit depressed insulin-stimulated increases in leg vascular conductance, skeletal muscle capillary perfusion, and Akt phosphorylation. Notably, we found that within individuals with T2D, those with lesser increases in leg vascular conductance in response to insulin exhibited the lowest increases in muscle capillary perfusion, suggesting that limited muscle capillary perfusion may be, in part, linked to the impaired ability of the upstream resistance vessels to dilate in response to insulin. Furthermore, we show that the eight-week walking intervention, which did not evoke weight loss, was insufficient to ameliorate skeletal muscle microvascular insulin resistance in previously sedentary, overweight/obese subjects with T2D, despite high adherence and tolerance. However, the walking intervention did improve (P&lt;0.05) popliteal artery flow-mediated dilation (+4.52%) and reduced HbA1c (-0.75%). It is possible that physical activity interventions that are longer in duration, engage large muscle groups with recruitment of the maximum number of muscle fibers, and lead to a robust reduction in metabolic risk factors may be required to overhaul microvascular insulin resistance in T2D. </jats:p>

Ameliorative effects of chickpea flavonoids on redox imbalance and mitochondrial complex I dysfunction in type 2 diabetic rats

“…Insulin resistance (IR), a hallmark of type 2 diabetes (T2D), is characterized by a blunted ability of peripheral tissues to regulate glucose homeostasis in response to insulin. 26 As shown in Fig. 2B-D, the FINS and HOMA-IS levels were markedly reduced ( p < 0.01), whereas HOMA-IR was substantially increased ( p < 0.01) in the DM control group compared with the NC group.…”

Nutrition Interactions With Exercise Training on Endothelial Function

“…Indeed, work by Park et al . (7) observed little to no weight loss after 8 wk of walking and no benefit to the microvascular. The benefit seen in popliteal artery FMD was observed under fasting conditions and likely reflects shear-stress–induced increases in NO bioavailability.…”

“…Few studies exist testing the efficacy of exercise with nutrition manipulation on microvascular insulin sensitivity. However, new work has examined the effect of insulin infusion on microvascular blood flow in adults with T2D after 8 wk of a standard low to moderate intensity walking exercise intervention (e.g., 150 min•wk −1 of moderate intensity exercise) without weight loss (7). Somewhat surprisingly, despite exercise raising fasting popliteal artery FMD without weight loss, there was no effect at the level of the microvascular during insulin stimulation.…”

“…Improving these CVD indexes may result in enhanced blood flow and decreased blood pressure in some, but not all, individuals given they are nontraditional risk factors for atherosclerosis (4,5). Exercise also has been shown to enhance microvascular circulation/ function (6,7), which often is impaired in individuals with chronic disease (8). However, recent work has highlighted that variations in energy intake after exercise interventions (e.g., 3-5 d•wk ˗1 of aerobic exercise at 60%-85% HR max ) may influence body weight (9).…”

Hyperinsulinemia blunts sympathetic vasoconstriction: a possible role of β-adrenergic activation

“…Insulin, in addition to its role on cellular glucose uptake, has vasodilatory effects that increase delivery of insulin and glucose to tissues such as skeletal muscle (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In the context of insulin-mediated peripheral vasodilation, counterregulatory mechanisms are required to maintain blood pressure and one such key mechanism is sympathetic activation.…”