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diabetic neuropathy results in vasomotor dysfunction of medium sized peripheral arteries

World Journal of Clinical Cases 2023年第22期11卷 5244-5251页

作者： Fahrettin Ege Ömer Kazci Sonay Aydin Department of Neurology VM Medicalpark HospitalAnkara 063200Turkey Department of Radiology Ankara Training and Research HospitalAnkara 063200Turkey Department of Radiology Erzincan Binali Yıldırım University Faculty of MedicineErzincan 063200Turkey

BACKGROUND The effect of the sympathetic nervous system on peripheral arteries causes vasoconstriction when smooth muscle cells in the walls of blood vessels contract,which leads to narrowing of arteries and reduction of the blood flow.AIM To compare sympathetic vasomotor activation of the brachial arteries in healthy subjects and patients with painful diabetic neuropathy;and therefore,to assess whether there is significant vasomotor dysfunction of medium sized arteries in diabetic neuropathy.METHODS The study included 41 diabetic neuropathy patients and 41 healthy controls.Baseline diameter and flow rate of the brachial arteries were measured.Then,using a bipolar stimulus electrode,a 10 mA,1 Hz electrical stimulus was administered to the median nerve at the wrist level for 5 s.The brachial artery diameter and blood flow rate were re-measured after stimulation.RESULTS In the control group,the median flow rate was 70.0 mL/min prior to stimulation and 35.0 mL/min after stimulation,with a statistically significant decrease(Pdiabetic neuropathy group,median flow rate before the stimulation was 35.0 mL/min.After stimulation,the median flow rate was 77.0 mL/min;thus,no significant decrease in the flow rate was detected.In the control group,the median brachial artery diameter,which was 3.6 mm prior to stimulation,decreased to 3.4 mm after stimulation,and this decrease was also statistically significant(P=0.046).In the diabetic neuropathy group,the median brachial artery diameter increased from 3.4 mm to 3.6 mm following nerve stimulation.Once again,no narrowing was observed.CONCLUSION Our research suggests that diabetic neuropathy results in significant vasomotor dysfunction of medium sized peripheral arteries.Physiological vasoconstriction in response to sympathetic activation is impaired in diabetic neuropathy.

关键词： diabetic neuropathy Vasomotor Dysfunction Peripheral arteries Doppler ultrasound

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Issues and challenges in diabetic neuropathy management:A narrative review

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World Journal of Diabetes 2023年第6期14卷 741-757页

作者： Che Aishah Nazariah Ismail Department of Physiology School of Medical SciencesUniversity Sains Malaysia Health CampusKubang Kerian 16150KelantanMalaysia

diabetic neuropathy(DN)is a devastating disorder with an increasing prevalence globally.This epidemic can pose a critical burden on individuals and communities,subsequently affecting the productivity and economic output of a country.With more people living a sedentary lifestyle,the incidence of DN is escalating worldwide.Many researchers have relentlessly worked on ways to combat this devastating disease.Their efforts have given rise to a number of commercially available therapies that can alleviate the symptoms of DN.Unfortunately,most of these therapies are only partially effective.Worse still,some are associated with unfavorable side effects.This narrative review aims to highlight current issues and challenges in the management of DN,especially from the perspective of molecular mechanisms that lead to its progression,with the hope of providing future direction in the management of DN.To improve the approaches to diabetic management,the suggested resolutions in the literature are also discussed in this review.This review will provide an in-depth understanding of the causative mechanisms of DN,apart from the insights to improve the quality and strategic approaches to DN management.

关键词： diabetic neuropathy Pathophysiology diabetic management diabetic medication

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Apigenin ameliorates diabetic neuropathy in rats by modulating the TLR4/MyD88 signaling pathway

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Asian Pacific Journal of Tropical Biomedicine 2023年第11期13卷 469-478,I0003,I0004,I0005,I0006,I0008页

作者： Yan-Bo Yu Mi-Zhen Qiu Da-Ying Zhang Department of Pain The First Affiliated Hospital of Nanchang UniversityNanchang 330006China

Objective:To determine the neuroprotective effects of apigenin against streptozotocin(STZ)-induced diabetic neuropathy(DN).Methods:To induce DN,Wistar rats(150-200 g)were administered with STZ(55 mg/kg,i.p.).Then they were randomly assigned to various groups,viz.,normal,diabetic control,insulin(10 IU/kg,s.c.),apigenin(5,10,and 20 mg/kg,p.o.),and insulin(10 IU/kg)plus apigenin(20 mg/kg,p.o.).Various behavioral,biochemical,and molecular markers[tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-6,Toll-like receptor 4(TLR4),myeloid differentiation primary response 88(MyD88),and nuclear factor erythroid 2-related factor 2(Nrf2)]were assessed.Results:Apigenin(10 and 20 mg/kg,p.o.)substantially reduced plasma glucose levels,lipid profile,aspartate transaminase,alanine transaminase,glycated hemoglobin,and neural advanced glycation end products in STZ-induced DN rats(P<0.05).After apigenin intervention,STZ-induced changes in food and water intake,body weight,urine output,allodynia,hyperalgesia,and insulin levels were markedly improved(P<0.05).Neural antioxidant enzymes(superoxide dismutase and glutathione)and Na+K+ATPase activity were also considerably elevated(P<0.05)while the level of lipid peroxidation was diminished following apigenin therapy(P<0.05).Furthermore,apigenin markedly upregulated the Nrf2 mRNA level while downregulating the mRNA expressions of TNF-αand ILs and the protein expressions of TLR4 and MyD88(P<0.05).STZ-induced histological abnormalities in the sciatic nerve were also improved by apigenin treatment.Conclusions:Apigenin exerts its neuroprotective effect by modulating the inflammatory and oxidative stress pathways via regulating the TLR4-MyD88 signaling pathway.

关键词： Apigenin diabetic neuropathy MyD88 Nrf2 Proinflammatory cytokines TLR4

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Soluble p75 neurotrophic receptor as a reliable biomarker in neurodegenerative diseases: what is the evidence?

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Neural Regeneration Research 2024年第3期19卷 536-541页

作者： Georges Jourdi Samuel Fleury Imane Boukhatem Marie Lordkipanidzé Research Center Montreal Heart InstituteMontrealQCCanada Faculty of Pharmacy Universitéde MontréalMontrealQCCanada UniversitéParis Cité INSERMInnovative Therapies in HaemostasisParisFrance Service d’Hématologie Biologique AP-HPHôpital LariboisièreParisFrance

Neurodegenerative diseases are often misdiagnosed,especially when the diagnosis is based solely on clinical symptoms.The p75 neurotrophic receptor(p75^(NTR))has been studied as an index of sensory and motor nerve development and maturation.Its cleavable extracellular domain(ECD)is readily detectable in various biological fluids including plasma,serum and urine.There is evidence for increased p75NTR ECD levels in neurodegenerative diseases such as Alzheimer’s disease,amyotrophic lateral sclerosis,age-related dementia,schizophrenia,and diabetic neuropathy.Whether p75^(NTR) ECD could be used as a biomarker for diagnosis and/or prognosis in these disorders,and whether it could potentially lead to the development of targeted therapies,remains an open question.In this review,we present and discuss published studies that have evaluated the relevance of this emerging biomarker in the context of various neurodegenerative diseases.We also highlight areas that require further investigation to better understand the role of p75^(NTR) ECD in the clinical diagnosis and management of neurodegenerative disorders.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis biomarker dementia diabetic neuropathy nerve growth factor receptor(NGFR) neurodegeneration p75^(NTR) schizophrenia

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Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway

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Neural Regeneration Research 2016年第2期11卷 345-351页

作者： Qing-rong Li Zhuo Wang Wei Zhou Shou-rui Fan Run Ma Li Xue Lu Yang Ya-shan Li Hong-li Tan Qi, ng-hua Shao Hong-ying Yang Second Affiliated Hospital of Kunming Medical University Department of Clinical Laboratory Kunming Yunnan Province China Third People's Hospital of Yunnan Province Kunming Yunnan Province China

Epalrestat is a noncompetitive and reversible aldose reductase inhibitor used for the treatment of diabetic neuropathy. This study assumed that epalrestat had a protective effect on diabetic peripheral nerve injury by suppressing the expression of aldose reductase in peripheral nerves of diabetes mellitus rats. The high-fat and high-carbohydrate model rats were established by intraperitoneal injection of streptozotocin. Peripheral neuropathy occurred in these rats after sustaining high blood glucose for 8 weeks. At 12 weeks after streptozotocin injection, rats were intragastrically administered epalrestat 100 mg/kg daily for 6 weeks. Transmission electron microscope revealed that the injuries to myelinated nerve fibers, non-myelinated nerve fibers and Schwann cells of rat sciatic nerves had reduced compared to rats without epalrestat administuation. Western blot assay and immunohistochemical results demonstrated that after intervention with epalrestat, the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase gradually increased, but aldose reductase protein expression gradually diminished. Results confirmed that epalrestat could protect against diabetic peripheral neuropathy by relieving oxidative stress and suppressing the polyol pathway.

关键词： nerve regeneration peripheral nerve injury streptozotocin reactive oxygen species diabetic neuropathy oxidative stress aldosereductase antioxidant enzymes polyol pathway aldose reductase inhibitor superoxide dismutase catalase glutathione peroxidase rats NSFCgrant neural regeneration

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Risk factors and pain status due to diabetic neuropathy in chronic long-term diabetic patients in a Chinese urban population

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Chinese Medical Journal 2012年第23期125卷 4190-4196页

作者： JI Na ZHANG Nan REN Zhan-jie JIA Ke-bao WANG Li NI Jia-xiang MA Jun Department of Pain Management Xuanwu Hospital Capital MedicaJ University Beijing 100053 China Department of Endocrinology Xuanwu Hospital Capital MedicaJ University Beijing 100053 China Department of Anesthesiology Xuanwu Hospital Capital MedicaJ University Beijing 100053 China Department of Urology Second Affiiated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China

Background With economic growth and urbanization there have been significant changes in the life style and diet of urban residents in large cities of China, which is experiencing a rapid increase in the prevalence of diabetes. While high prevalence of diabetes has been reported, little is known of the long-term effects of diabetes in such a large population. The aim of this study was to estimate the morbidity rate of diabetic peripheral neuropathy （DPN） in a Chinese urban diabetic population with more than 10 years＇ disease duration, and evaluate the relevant risk factors. The clinical manifestation of DPN and pain status was also assessed. Methods Five hundred and sixty-five diabetes patients were recruited into the study. Symptoms and examination helped diagnose neuropathy. The clinical manifestation of DPN was assessed with a visual analog pain score （VAS）. diabetic complication status was determined from medical records. Serum lipids and lipoproteins, glycosylated hemoglobin （HbAlc）, and the urinary albumin excretion rate were measured. Results The morbidity rate of DPN was 46.6%. HbAlc, hyperlipidemia, and retinopathy were significantly associated with neuropathy, and these risk factors were correlated with other diabetic micro and/or macrovascular complications. The average VAS pain score of the DPN patients was 4.12＋2.07. Severe and moderate pain was experienced by 11.4% and 40.5% respectively of DPN patients. About 3.7% of diabetic subjects had lower limb ulcer or amputation. Conclusions The morbidity rate of DPN for diabetic patients with 〉10 years duration is very high compared to the range reported for other populations in the world. The risk factors for DPN include HbAlc, hyperlipidemia, and retinopathy. In long-standing diabetic patients, DPN was not associated with diabetic duration, and half of the DPN patients experienced considerable daily suffering.

关键词： diabetic neuropathy risk factors pain status urban Chinese population

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Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy

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Chinese Medical Journal 2004年第9期117卷 1317-1320页

作者：黄一宁贾志荣石昕孙相如 Department of Neurology First Hospital of Peking University Beijing 100034 China

Background diabetic neuropathy is common in diabetes mellitus. The early stage of diabetic neuropathy is often symptomless and difficult to be treated. The aim of this study was to assess the correlation between the results of the sympathetic skin response (SSR) test and the development of diabetic neuropathy, and explore the use of SSR as an objective basis for the early diagnosis of diabetic neuropathy. Methods The latencies and amplitudes of initiation and of the N and P waves were determined by SSR testing of the extremities of 80 diabetic patients and 30 healthy controls. Results The latencies of initiation and of the N and P waves were significantly (Pdiabetic patients than in the controls, while there was no significant difference in the amplitudes (P>0.05). All but two patients (97.5%) demonstrated abnormal SSR in at least one limb. Conclusions SSR can detect early dysfunction of the small sympathetic fibers in people affected by diabetes mellitus, and may be a useful electrophysiological test for the early diagnosis of diabetic neuropathy.

关键词： diabetic neuropathy peripheral nervous system disease electrophysiology sympathetic skin response sympathetic nervous system

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Enteric neuropathy in diabetes:Implications for gastrointestinal function

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World Journal of Gastroenterology 2024年第22期30卷 2852-2865页

作者： Mona Mohamed Ibrahim Abdalla Department of Human Biology School of MedicineInternational Medical UniversityBukit Jalil 57000Kuala LumpurMalaysia

Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

关键词： diabetic neuropathy Gastrointestinal Insulin resistance Diabetes Enteric nervous system Enteric neuropathy

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Molsidomine ameliorates diabetic peripheral neuropathy complications in Wistar rats

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Animal Models and Experimental Medicine 2021年第3期4卷 243-248页

作者： Pranav Nayak B Minaz Nathani Khadar Pasha Pharmacology Department and Al-Ameen College of Pharmacy and Rajiv Gandhi University BangaloreIndia

diabetic neuropathy is a disorder which affects various regions of the nervous sys-tem and there is no specific treatment available for it.So,the present study eval-uated protective effect of molsidomine in diabetic neuropathy in rats.Diabetes was induced in male Wistar rats by administrating streptozotocin(52 mg/kg i.p).diabetic rats were administered with molsidomine 5 mg/kg p.o,and 10mg/kg p.***.as treatment.After 8 weeks of treatment,Motor coordination,Mechanical allodynia,Mechanical hyperalgesia,Nerve conduction velocity,Glycosylated hemoglobin were assessed.Thereafter animals were sacrificed and sciatic nerve was isolated.It was used for reduced glutathione,lipid peroxidation and for histopathology.Treatment with molsidomine significantly improved motor coordination,paw withdrawal threshold,mechanical threshold and nerve conduction velocity.Furthermore,mol-sidomine treatment also reduced malondialdehyde levels and prevented depletion of reduced glutathione in sciatic nerve homogenate.Histopathology shows molsid-omine treatment maintained normal architecture of sciatic nerve.The results of our study strengthens the alterative use of molsidomine in diabetic neuropathy.

关键词： diabetic neuropathy molsidomine streptozotocin Wistar rats

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Effects of selenium on electrophysiological changes associated with diabetic peripheral neuropathy

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Neural Regeneration Research 2011年第8期6卷 617-622页

作者： Murat Ayaz Hülagu Kaptan Department of Biophysics Seluklu Medical FacultySelcuk University Department of Neurosurgery Seluklu Medical FacultySelcuk University

Our previous study has demonstrated that sodium selenite prevents oxidative stress, suggesting that selenium can improve diabetic peripheral neuropathy. Results from this study demonstrated that diabetes mellitus resulted in significant increased time to peak, as well as rheobase and chronaxie values. In addition, maximum depolarization, area under compound action potential, kinetics, and conduction velocities of fast and slow nerve fiber groups were decreased. Sodium selenite exhibited positive effects on alterations of diabetes mellitus-induced conduction velocity distribution. This neuroprotective effect was primarily observed in the area under compound action potential and compound action potential kinetic waveforms, as well as rheobase and chronaxie. Results from this study showed that selenium supplementation blocked the diabetes mellitus-induced shift of actively contributing nerve fibers, and restored levels towards age-matched control group values. Chronic selenate supplementation for experimental diabetic peripheral neuropathy exhibited protective effects in measured electrophysiological parameters.

关键词： sciatic nerve diabetic neuropathy streptozotocin conduction velocity distribution sodium selenite

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