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

Author(s)

Park, Lauren K. ^{[1, 2]} ; Parks, Elizabeth J. ^{[1, 3]} ; Pettit-Mee, Ryan J. ^{[1, 2]} ; Woodford, Makenzie L. ^{[1, 2]} ; Ghiarone, Thaysa ^[2] ; Smith, James A. ^{[1, 2]} ; Sales, Allan R. K. ^{[4, 5, 2]} ; Martinez-Lemus, Luis A. ^{[2, 6]} ; Manrique-Acevedo, Camila ^{[7, 2, 8]} ; Padilla, Jaume ^{[1, 2]}

Affiliation

^[1] Univ Missouri, Dept Nutr & Exercise Physiol, Columbia, MO 65211 - USA

^[2] Univ Missouri, Dalton Cardiovasc Res Ctr, Columbia, MO 65211 - USA

^[3] Univ Missouri, Dept Med, Div Gastroenterol & Hepatol, Columbia, MO - USA

^[4] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo - Brazil

^[5] DOr Inst Res & Educ IDOR, Sao Paulo - Brazil

^[6] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO - USA

^[7] Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 - USA

^[8] Univ Missouri, Dept Med, Div Endocrinol Diabet & Metab, Columbia, MO - USA

• Document type: Journal article
• Source: Journal of Applied Physiology; v. 129, n. 2, p. 283-296, AUG 2020.
• Web of Science Citations: 0

Abstract

We aimed to examine whether 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 whether T2D-associated skeletal muscle microvascular insulin resistance, as well as overall vascular dysfunction, would be ameliorated by an 8-wk walking intervention (45 min 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 8-wk 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 < 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. NEW \& NOTEWORTHY This report provides evidence that in sedentary subjects with type 2 diabetes diminished insulin-stimulated increases in leg vascular conductance and ensuing blunted capillary perfusion in skeletal muscle are not restorable by increased walking alone. More innovative physical activity interventions that ultimately result in a robust mitigation of metabolic risk factors may be vital for reestablishing skeletal muscle microvascular insulin sensitivity in type 2 diabetes. (AU)

• FAPESP's process: 17/25613-6 - Habitual aerobic exercise decreases endothelin-1 and restores insulin-induced vasodilation in patients with type 2 diabetes: role shear stress
• Grantee: Allan Robson Kluser Sales
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/11671-6 - Effect of high intensity interval training versus continuous moderate in the peripheral reflex mechanisms of control of the sympathetic activity in patients with heart failure
• Grantee: Allan Robson Kluser Sales
• Support Opportunities: Scholarships in Brazil - Post-Doctoral