scholarly journals Diabetic Peripheral Neuropathy Increases Electrical Stimulation Threshold of Sciatic Nerve: A Prospective Parallel Cohort Study

2020 ◽  
Vol Volume 13 ◽  
pp. 4447-4455
Author(s):  
Guang Ying Zhang ◽  
Yi Feng Chen ◽  
Wei Xin Dai ◽  
Dan Zhang ◽  
Yi Huang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Electrical Stimulation ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Diabetic Peripheral Neuropathy ◽  
Stimulation Threshold

scholarly journals Endothelin-1 predicts incident diabetic peripheral neuropathy in Type 2 Diabetes: a cohort study

2020 ◽  
Vol 182 (4) ◽  
pp. 429-438
Author(s):  
Sharon Li Ting Pek ◽  
Su Chi Lim ◽  
Keven Ang ◽  
Pek Yee Kwan ◽  
Wern Ee Tang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Cohort Study ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Diabetes Duration ◽  
Endothelin 1

Introduction Diabetic peripheral neuropathy (DPN) is a common microvascular complication in patients with type 2 diabetes (T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, implicated in the causal pathway of microangiopathy. We investigated whether baseline plasma endothelin-1 and other metabolic and vascular risk factors predicted the incidence of DPN. Design This is a 3-year observational, cohort study. Methods In patients with T2D (n = 2057), anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements. Forearm cutaneous endothelial reactivity was assessed by iontophoresis and laser Doppler flowmetry/imaging. Measurements were repeated on follow-up. Incident DPN was considered present if an abnormal finding in monofilament (<8 of 10 points) or neurothesiometer testing was ≥25 volts on either foot at 3-year follow-up, but normal at baseline. Plasma endothelin-1 was assessed by ELISA. Results At baseline, mean age of patients was 57.4 ± 10.8 years old and prevalence of DPN was 10.8%. Of the 1767 patients without DPN, 1250 patients returned for follow-up assessment ((2.9 ± 0.7) years), with a 10.7% incidence of DPN. Patients with incident DPN had significantly higher baseline endothelin-1 (1.43 (1.19–1.73) vs 1.30 (1.06–1.63)) pg/mL, P < 0.0001. Multivariable Cox proportional hazards ratio showed a 1-s.d. increase in log endothelin-1 (adjusted HR: 4.345 (1.451–13.009), P = 0.009), systolic blood pressure (per 10-unit) (adjusted HR: 1.107 (1.001–1.223), P = 0.047) and diabetes duration (adjusted HR: 1.025 (1.004–1.047), P = 0.017) predicted incident DPN, after adjustment for glycemic control, eGFR, albuminuria, peripheral arterial disease and retinopathy status. Conclusion Higher baseline endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of endothelin-1 in DPN.

scholarly journals Neuroprotective Effect of Salvianolic Acid A against Diabetic Peripheral Neuropathy through Modulation of Nrf2

2020 ◽  
Vol 2020 ◽  
pp. 1-22 ◽  
Author(s):  
Chunyang Xu ◽  
Biyu Hou ◽  
Ping He ◽  
Peng Ma ◽  
Xinyu Yang ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Mrna Expression ◽  
Mitochondrial Function ◽  
Diabetic Peripheral Neuropathy ◽  
Nuclear Translocation ◽  
Related Factor ◽  
Inflammatory Factor ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Oxidative stress has been recognized as the contributor to diabetic peripheral neuropathy (DPN). Antioxidant strategies have been most widely explored; nevertheless, whether antioxidants alone prevent DPN still remains inconclusive. In the present study, we established an in vitro DPN cell model for drug screening using Schwann RSC96 cells under high glucose (HG) stimulation, and we found that salvianolic acid A (SalA) mitigated HG-induced injury evidenced by cell viability and myelination. Mechanistically, SalA exhibited strong antioxidative effects by inhibiting 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing reactive oxygen species (ROS), malondialdehyde (MDA), and oxidized glutathione (GSSG) content, as well as upregulating antioxidative enzyme mRNA expression. In addition, SalA significantly extenuated neuroinflammation with downregulated inflammatory factor mRNA expression. Furthermore, SalA improved the mitochondrial function of HG-injured Schwann cells by scavenging mitochondrial ROS, decreasing mitochondrial membrane potential (MMP), and enhancing ATP production, as well as upregulating oxidative phosphorylation gene expression. More importantly, we identified nuclear factor-E2-related factor 2 (Nrf2) as the upstream regulator which mediated protective effects of SalA on DPN. SalA directly bound to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) and thus disrupted the interaction of Nrf2 and Keap1 predicted by LibDock of Discovery Studio. Additionally, SalA significantly inhibited Nrf2 promoter activity and downregulated Nrf2 mRNA expression but without affecting Nrf2 protein expression. Interestingly, SalA upregulated the nuclear Nrf2 expression and promoted Nrf2 nuclear translocation by high content screening assay, which was confirmed to be involved in its antiglucotoxicity effect by the knockdown of Nrf2 in RSC96 cells. In KK-Ay mice, we demonstrated that SalA could effectively improve the abnormal glucose and lipid metabolism and significantly protect against DPN by increasing the mechanical withdrawal threshold and sciatic nerve conduction velocity and restoring the ultrastructural impairment of the injured sciatic nerve induced by diabetes. Hence, SalA protected against DPN by antioxidative stress, attenuating neuroinflammation, and improving mitochondrial function via Nrf2. SalA may be prospective therapeutics for treating DPN.

scholarly journals Protection of Trigonelline on Experimental Diabetic Peripheral Neuropathy

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ji-Yin Zhou ◽  
Shi-Wen Zhou
Keyword(s):  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Nerve Conduction ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Conduction Velocity ◽  
Diabetic Rats ◽  
Beneficial Effects ◽  
Mitogen Activated Protein ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The mechanisms leading to diabetic peripheral neuropathy are complex and there is no effective drug to treat it. As an active component of several traditional Chinese medicines, trigonelline has beneficial effects on diabetes with hyperlipidemia. The protective effects and the mechanism of trigonelline on diabetic peripheral neuropathy were evaluated in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Rats were divided into four groups at the end of week 2: control, diabetes, diabetes + trigonelline (40 mg/kg), and diabetes + sitagliptin (4 mg/kg). After 48-week treatment, technologies of nerve conduction, cold and hot immersion test, transmission electron microscopy, real-time PCR, and Western blotting were applied. Serum glucose, serum insulin, insulin sensitivity index, lipid parameters, body weight, sciatic nerve conduction velocity, nociception, glucagon-like peptide-1 receptor mRNA and protein, total and phosphorylated p38 mitogen-activated protein kinases protein expression, malonaldehyde content, and superoxide dismutase activity were altered in diabetic rats, and were near control levels treated with trigonelline. Slight micropathological changes existed in sciatic nerve of trigonelline-treated diabetic rats. These findings suggest that trigonelline has beneficial effects for diabetic peripheral neuropathy through glucagon-like peptide-1 receptor/p38 mitogen-activated protein kinases signaling pathway, nerve conduction velocity, antioxidant enzyme activity, improving micropathological changes of sciatic nerve and decreasing lipid peroxidation.

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