scholarly journals Reducing monocarboxylate transporter MCT1 worsens experimental diabetic peripheral neuropathy

2020 ◽  
Author(s):  
Mithilesh Kumar Jha ◽  
Xanthe Heifetz Ament ◽  
Fang Yang ◽  
Ying Liu ◽  
Michael J. Polydefkis ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Neuropathy ◽  
Peripheral Nerve ◽  
Diabetic Peripheral Neuropathy ◽  
Peripheral Nerve Regeneration ◽  
Metabolic Energy ◽  
Monocarboxylate Transporter ◽  
Diabetic Patients ◽  
Wild Type ◽  
Monocarboxylate Transporter 1

AbstractDiabetic peripheral neuropathy (DPN) is one of the most common complications in diabetic patients. Though the exact mechanism for DPN is unknown, it clearly involves metabolic dysfunction and energy failure in multiple cells within the peripheral nervous system (PNS). Lactate is an alternate source of metabolic energy that is increasingly recognized for its role in supporting neurons. The primary transporter for lactate in the nervous system, monocarboxylate transporter-1 (MCT1), has been shown to be critical for peripheral nerve regeneration and metabolic support to neurons/axons. In this study, MCT1 was reduced in both sciatic nerve and dorsal root ganglia in wild-type mice treated with streptozotocin (STZ), a common model of type-1 diabetes. Heterozygous MCT1 null mice treated with STZ developed a more severe DPN compared to wild-type mice, as measured by greater axonal demyelination, decreased peripheral nerve function, and increased numbness to innocuous low-threshold mechanical stimulation. Given that MCT1 inhibitors are being developed as both immunosuppressive and chemotherapeutic medications, our results suggest that clinical development in patients with diabetes should proceed with caution. Collectively, our findings uncover an important role for MCT1 in DPN and provide a potential lead toward developing novel treatments for this currently untreatable disease.

scholarly journals Altered Achilles tendon function during walking in people with diabetic neuropathy: implications for metabolic energy saving

2018 ◽  
Vol 124 (5) ◽  
pp. 1333-1340 ◽  
Author(s):  
M. Petrovic ◽  
C. N. Maganaris ◽  
K. Deschamps ◽  
S. M. Verschueren ◽  
F. L. Bowling ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Achilles Tendon ◽  
Energy Saving ◽  
Diabetic Peripheral Neuropathy ◽  
Energy Savings ◽  
Metabolic Cost ◽  
Metabolic Energy ◽  
Diabetic Patients ◽  
Length Changes ◽  
Diabetes Patients

The Achilles tendon (AT) has the capacity to store and release elastic energy during walking, contributing to metabolic energy savings. In diabetes patients, it is hypothesized that a stiffer Achilles tendon may reduce the capacity for energy saving through this mechanism, thereby contributing to an increased metabolic cost of walking (CoW). The aim of this study was to investigate the effects of diabetes and diabetic peripheral neuropathy (DPN) on the Achilles tendon and plantarflexor muscle-tendon unit behavior during walking. Twenty-three nondiabetic controls (Ctrl); 20 diabetic patients without peripheral neuropathy (DM), and 13 patients with moderate/severe DPN underwent gait analysis using a motion analysis system, force plates, and ultrasound measurements of the gastrocnemius muscle, using a muscle model to determine Achilles tendon and muscle-tendon length changes. During walking, the DM and particularly the DPN group displayed significantly less Achilles tendon elongation (Ctrl: 1.81; DM: 1.66; and DPN: 1.54 cm), higher tendon stiffness (Ctrl: 210; DM: 231; and DPN: 240 N/mm), and higher tendon hysteresis (Ctrl: 18; DM: 21; and DPN: 24%) compared with controls. The muscle fascicles of the gastrocnemius underwent very small length changes in all groups during walking (~0.43 cm), with the smallest length changes in the DPN group. Achilles tendon forces were significantly lower in the diabetes groups compared with controls (Ctrl: 2666; DM: 2609; and DPN: 2150 N). The results strongly point toward the reduced energy saving capacity of the Achilles tendon during walking in diabetes patients as an important factor contributing to the increased metabolic CoW in these patients. NEW & NOTEWORTHY From measurements taken during walking we observed that the Achilles tendon in people with diabetes and particularly people with diabetic peripheral neuropathy was stiffer, was less elongated, and was subject to lower forces compared with controls without diabetes. These altered properties of the Achilles tendon in people with diabetes reduce the tendon’s energy saving capacity and contribute toward the higher metabolic energy cost of walking in these patients.

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

scholarly journals Albumin-Creatinine Ratio is More Diagnostic Sensitive than Cystatin-C in Assessment of Diabetic Peripheral Neuropathy

2018 ◽  
Vol 1 (3) ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Peripheral Neuropathy ◽  
Cystatin C ◽  
Early Treatment ◽  
Diabetic Peripheral Neuropathy ◽  
Diabetic Patients ◽  
Creatinine Ratio ◽  
Serum Cystatin C ◽  
Albumin Creatinine Ratio

Background: Diabetic Peripheral neuropathy is one of the most common cardiovascular complications among diabetes mellitus patients and occurs in more than half of the population of diabetic patients world-wide. It is a common cause of foot ulcer, gangrene and amputation among diabetics. Thus, its prevention or early treatment can improve the quality of life of diabetic patients. In a bid to reduce it, various biochemical markers have been evaluated to enable early treatment and amelioration of diabetic neuropathy among diabetes mellitus patients. Aim: Evaluation of the diagnostic relevance of Cystatin-C versus Albumin-creatinine ratio in assessment of Peripheral neuropathy in diabetic type 2 subjects. Method: 102 type 2 DM subjects (66 females and 36 males) and 100 control subjects of same age range (40 – 80 years) were recruited for this study which includes 51 subjects with peripheral neuropathy and 51 subjects without peripheral neuropathy. Serum Cystatin-C, Microalbuminuria, Urine creatinine and HBA1c were analysed with standard methods. Results: Cystatin-C, Microalbuminuria, Albumin-creatinine ratio and Glycated haemoglobin were significantly elevated (P<0.05) in diabetic subjects compared to the control. Cystatin-C (ng/ml), microalbuminuria (mg/l), albumin creatinine ratio (mg/mmol) and HBA1c (%) is [105.52 ± 45.11; 90.07±20.29; 10.48 ± 4.82; 6.9±1.7] respectively. Microalbuminuria, albumin creatinine ratio showed significant increase (P<0.05) in subjects with peripheral neuropathy compared to those subjects without [92.11± 22.82; 35.70±16.35; 2.61±1.1; 6.38±1.79]. The ROC curve shows that Albumin-creatinine ratio showed significant (P<0.05) sensitivity to peripheral neuropathy [AUC=0.714] while Cystatin-C showed no significant (P<0.05) sensitivity to peripheral neuropathy complication [AUC=0.553]. Conclusion: Cystatin-C was found to be deranged in diabetics. However, Albumin-creatinine ratio showed more diagnostic sensitivity for peripheral neuropathy than Cystatin-C.

A Case of Fever and a Wrist Drop

2018 ◽  
pp. 69-74
Author(s):  
Aaron E. Miller ◽  
Tracy M. DeAngelis ◽  
Michelle Fabian ◽  
Ilana Katz Sand
Keyword(s):  
Nervous System ◽  
Gastrointestinal Tract ◽  
Peripheral Neuropathy ◽  
Peripheral Nerve ◽  
Polyarteritis Nodosa ◽  
Joint Pain ◽  
Immunosuppressive Agents ◽  
Nerve Biopsy ◽  
Definitive Diagnosis ◽  
Wrist Drop

Polyarteritis nodosa (PAN) is a systemic illness that most often involves the skin, kidneys, and gastrointestinal tract, in addition to the peripheral nervous system. It most often affects middle-aged individuals, men more than women. The particular type of peripheral neuropathy is often mononeuropathy or mononeuritis multiplex—a condition in which there is discrete involvement of multiple individual nerves. Definitive diagnosis of the vascular nature of the neuropathy requires peripheral nerve biopsy, which will demonstrate inflammation throughout the walls of small and medium-sized arteries. The CNS is also frequently involved in PAN. Constitutional symptoms, including fever, fatigue, and diffuse muscle and joint pain, are common and raise the suspicion of a systemic illness. Treatment generally involves the use of corticosteroids and immunosuppressive agents such as cyclophosphamide or azathioprine.

scholarly journals Diabetic Peripheral Neuropathy: Epidemiology, Physiopathology, Diagnosis and Treatment

2019 ◽  
Vol 7 (1) ◽  
pp. 35-48
Author(s):  
Nazma Akter
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Clinical Evidence ◽  
Current Treatment ◽  
Diabetic Patients ◽  
First Line ◽  
Diabetic Neuropathic Pain ◽  
Current Treatment Regimen ◽  
Limb Proprioception

Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and type 2 diabetes. It affects over 90% of the diabetic patients. It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication, but several other hypotheses have been postulated. It is typically characterized by significant deficits in tactile sensitivity, vibration sense, lower-limb proprioception, and kinesthesia. Painful DPN has been shown to be associated with significant reductions in overall quality of life, increased levels of anxiety and depression, sleep impairment, and greater gait variability. DPN is often misdiagnosed and inadequately treated. Clinical recognition of DPN is imperative for allowing timely symptom management to reduce the morbidity associated with this condition. The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy, improving glycemic control as a prophylactic therapy and using medications to alleviate pain. First line drugs for pain relief include anticonvulsants, such as pregabalin and gabapentin and antidepressants, especially those that act to inhibit the reuptake of serotonin and noradrenaline. In addition, there is experimental and clinical evidence that opioids can be helpful in pain control, mainly if associated with first line drugs. Other agents, including for topical application, such as capsaicin cream and lidocaine patches, have also been proposed to be useful as adjuvant in the control of diabetic neuropathic pain, but the clinical evidence is insufficient to support their use. The purpose of this review is to examine proposed mechanisms of DPN, summarize current treatment regimen. A better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies. Delta Med Col J. Jan 2019 7(1): 35-48

scholarly journals The Effects of Combined Exercise Training (Resistance-Aerobic) on Serum Kinesin and Physical Function in Type 2 Diabetes Patients with Diabetic Peripheral Neuropathy (Randomized Controlled Trials)

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Seyedeh Hoda Seyedizadeh ◽  
Sadegh Cheragh-Birjandi ◽  
Mohammad Reza Hamedi Nia
Keyword(s):  
Type 2 Diabetes ◽  
Peripheral Neuropathy ◽  
Exercise Training ◽  
Physical Function ◽  
Diabetic Peripheral Neuropathy ◽  
Diabetic Patients ◽  
Combined Exercise ◽  
Combined Exercise Training ◽  
Diabetes Patients

Diabetic peripheral neuropathy is one of the most common chronic complications of diabetics which causes nerve damage and muscle strength decrease in patients. This in turn results in imbalance leading to the diabetic patients’ daily activity disparity. The present investigation was conducted to specifically study the effects of combined training (resistance-aerobic) on serum kinesin-1 and physical function in type 2 diabetes patients with diabetic peripheral neuropathy. 24 diabetic neuropathic females were randomly to be selected out and divided into two experimental and control groups. The experimental group received resistance-aerobic training for 3 sessions during eight weeks. The exercise training included resistance exercises with 2-3 sets, 6-7 exercise stations, 8-12 repetitions (reps), and 3-5 minutes of rest in between the exercises, and the aerobic exercises contained 50-65% of heart rate reserve (HRR) for 3 minutes with 30 seconds of rest interval between sets and 5-10 repetitions. Results show that the serum kinesin-1 level and aerobic endurance declined after eight weeks of combined (resistance-aerobic) exercise training, but this decrease was not significant. The upper body strength increased but it was not significant, while the lower body showed a significant strength increase. With regard to the progressive nature of diabetic peripheral neuropathy, it seems that even the little changes resulting from the combined exercise training can be useful. Nevertheless, more research is required in this area.

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