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Enhanced skeletal muscle metaboreflex activation in type 2 diabetes
Author(s) -
Mizuno Masaki,
Holwerda Seth H,
Mitchell Jere H,
Smith Scott A,
Fadel Paul J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1004.3
Subject(s) - medicine , endocrinology , insulin resistance , type 2 diabetes , isometric exercise , skeletal muscle , insulin , blood pressure , diabetes mellitus , contraction (grammar) , streptozotocin
The effects of insulin on the central nervous system are becoming increasingly recognized. However, the impact of insulin resistance, as in type 2 diabetes (T2D) patients, on neural cardiovascular control mechanisms remains unclear. Herein, we examined the blood pressure (BP) and sympathetic responses to activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) in T2D patients (post exercise ischemia (PEI) following 40% maximum voluntary contraction isometric handgrip) and in Sprague Dawley rats with low‐dose streptozotocin and high‐fat diet induced T2D (hindlimb intra‐arterial capsaicin administration, 1 μg/100 μL). T2D patients exhibited exaggerated BP and muscle sympathetic nerve activity (SNA) responses during PEI compared to age, and bodyweight matched healthy controls (muscle SNA: T2D, Δ31.7 ± 4.9 vs. Control, Δ16.7 ± 3.6 burst/100 heartbeats, P=0.04). Likewise, in T2D rats, BP and renal SNA responses to capsaicin infusion were augmented compared to normal Sprague Dawley rats (renal SNA: T2D, 432 ± 133 vs. Control, 83 ± 25 units, P=0.003). In the T2D patient study, the greater pressor and muscle SNA response to PEI appeared to be related to insulin resistance (HOMA IR: mean BP, R=0.42, P=0.07; muscle SNA, r=0.602, P=0.006). To better understand the impact of these results, intra‐cerebroventricular (ICV) insulin injection was performed in Sprague Dawley rats. ICV insulin did not affect the pressor responses to muscle contraction. Collectively, these preliminary findings suggest that muscle metaboreflex activation is augmented in T2D and changes in insulin in the central nervous system may not be a primary mechanism. Support or Funding Information Supported by NIH‐088422 (S.A.S) and AHA‐ 20160072 (P.J.F.)