Type 2 Diabetes Elicits Lower Nitric Oxide, Bradykinin Concentration and Kallikrein Activity Together with Higher DesArg9-BK and Reduced Post-Exercise Hypotension Compared to Non-Diabetic Condition

The purposes of this study were to analyze and compare the effects of exercise performed in different intensities, above and below lactate threshold (LT) on post-exercise blood pressure (BP) and nitric oxide (NO) responses in individuals with type 2 diabetes (T2D). For this, 11 T2D underwent the following sessions: 1) control session; 2) 20-min of moderate cycling (80% LT); and 3) 20-min of high intensity cycling (120%LT) on a cycle ergometer. Plasma NO and BP measurements were carried out at rest and at 15 and 45 min of post-sessions. When compared to rest, only the exercise session performed at 120%LT elicited an increase of NO (from 7.2 to 9.5 µM, p<0.05), as well as a decrease in systolic BP (from 126.6±7.9 to 118.7±3.9 mmHg, p<0.05) during the post-exercise period. In conclusion, the results suggest that NO release and post-exercise BP decrease are intensity-dependent for individuals with T2D.

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Concomitant peripheral neuropathy and type 2 diabetes impairs post-exercise cutaneous perfusion and flowmotion

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab414 ◽

2021 ◽

Author(s):

Cécile Reynès ◽

Jean-Baptiste Beaume ◽

Françoise Latil-Plat ◽

Houda Ennaifer ◽

Laure Rocher ◽

...

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Peripheral Neuropathy ◽

Laser Doppler Flowmetry ◽

Blood Perfusion ◽

Laser Speckle ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Post Exercise

Abstract Aim The study investigated changes in microvascular perfusion during post-exercise recovery in those with type 2 diabetes, with or without peripheral neuropathy, as well as in healthy controls and those with obesity. Methods Skin blood perfusion was assessed in each group using laser doppler flowmetry and laser speckle contrast imaging before and immediately after a six-minute walking test. Laser doppler flowmetry recordings underwent wavelet transformation to allow specific control mechanisms of blood perfusion to be studied (e.g. endothelial nitric oxide independent and dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Results Skin blood perfusion increased after exercise in all groups (22.3±28.1% with Laser speckle contrast imaging and 22.1±52.5% with laser doppler flowmetry). Throughout post-exercise recovery, the decrease was blunted in those with subclinical peripheral neuropathy and confirmed peripheral neuropathy when compared to the other three groups. After exercise, total spectral power increased in all groups. The relative contributions of each endothelial band was lower in those with confirmed peripheral neuropathy than in the healthy controls and those with obesity (nitric oxide-dependent function: 23.6±8.9% versus 35.5±5.8% and 29.3±8.8%, respectively; nitric oxide-independent function: 49.1±23.7% versus 53.3±10.4% and 64.6±11.4%, respectively). The neurogenic contribution decreased less in those with confirmed peripheral neuropathy and in those with type 2 diabetes alone, compared to those with subclinical peripheral neuropathy and those with obesity (-14.5±9.9% and -12.2±6.1% versus -26.5±4.7% and -21.7±9.4%, respectively). Conclusion Peripheral neuropathy, whatever the stage, altered the microvascular response to exercise via impaired endothelial and neurogenic mechanisms.

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Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase

European Heart Journal ◽

10.1093/eurheartj/ehi876 ◽

2006 ◽

Vol 27 (10) ◽

pp. 1159-1165 ◽

Cited By ~ 36

Author(s):

Satoshi Yasuda ◽

Shunichi Miyazaki ◽

Munetake Kanda ◽

Yoichi Goto ◽

Masaaki Suzuki ◽

...

Keyword(s):

Nitric Oxide ◽

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Nitric Oxide Synthase ◽

Asymmetric Dimethylarginine ◽

Endogenous Inhibitor ◽

Oxide Synthase

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Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

Journal of Applied Physiology ◽

10.1152/japplphysiol.00286.2016 ◽

2017 ◽

Vol 122 (1) ◽

pp. 38-47 ◽

Cited By ~ 30

Author(s):

Leryn J. Reynolds ◽

Daniel P. Credeur ◽

Camila Manrique ◽

Jaume Padilla ◽

Paul J. Fadel ◽

...

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Blood Flow ◽

Vastus Lateralis ◽

Glucose Disposal ◽

Endothelin 1 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

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