scholarly journals Treatment of Streptozotocin-Induced Diabetic Rats with Alogliptin: Effect on Vascular and Neural Complications

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Brian Dake ◽  
Mark A. Yorek

We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.

2011 ◽  
Vol 120 (03) ◽  
pp. 132-138 ◽  
Author(s):  
A. Dieckmann ◽  
M. Kriebel ◽  
E. Andriambeloson ◽  
D. Ziegler ◽  
M. Elmlinger

AbstractDiabetic neuropathy is one of the most severe complications of diabetes, affecting approximately one-third of diabetic patients. We investigated the potential neuroprotective effect of Actovegin®, a deproteinized hemoderivative of calf blood, in an animal model of diabetic neuropathy.A single intravenous injection of streptozotocin (STZ, 55 mg/kg) was used to induce experimental diabetes in male Sprague-Dawley rats. Actovegin® (200 or 600 mg/kg) was administered intraperitoneally from day 11 to day 40 post-STZ exposure. N-acetylcysteine (NAC) was used as a positive control and was added to drinking water (0.2 g/l) from day 2 until day 40. Measurements to assess efficacy included sensory nerve conduction velocity (SNCV), intraepidermal nerve fiber density (IENFD), and poly(ADP-ribose) content.A decrease (35%) in sensory nerve conduction velocity (SNCV) was seen in STZ-induced diabetic rats from day 10 post-STZ administration and persisted at days 25 and 39. At study completion (day 41), a decrease (32%) in intraepidermal nerve fiber density (IENFD) was found in hind-paw skin biopsies from STZ-rats. Reduced SNCV and IENFD were significantly ameliorated by both doses of Actovegin®. More­over, 600 mg/kg Actovegin® markedly decreased poly(ADP-ribose) polymerase (PARP) activity in sciatic nerves from STZ-diabetic rats as assessed by poly(ADP-ribose) content.Actovegin® improved several para­meters of experimental diabetic neuropathy via mechanisms involving suppression of PARP activation, providing a rationale for treatment of this disease in humans.


2000 ◽  
Vol 1 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Heather Flint ◽  
Mary A. Cotter ◽  
Norman E. Cameron

Pentoxifylline has several actions that improve blood rheology and tissue perfusion and may therefore potentially be applicable to diabetic neuropathy. The aims of this study were to ascertain whether 2 weeks of treatment with pentoxifylline could correct nerve conduction velocity and blood flow deficits in 6-week streptozotocin-diabetic rats and to examine whether the effects were blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor,NG-nitro-ʟ-arginine. Diabetic deficits in sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial blood flow was approximately halved by diabetes and this deficit was 50.4% corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these actions of pentoxifylline on nerve conduction and blood flow whereasNG-nitro-ʟ-arginine was without effect. Thus, pentoxifylline treatment confers neurovascular benefits in experimental diabetic neuropathy, which are linked at least in part to cyclooxygenasemediated metabolism.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Saeko Asano ◽  
Tatsuhito Himeno ◽  
Tomohide Hayami ◽  
Mikio Motegi ◽  
Rieko Inoue ◽  
...  

Distal sensory-motor polyneuropathy is one of the most frequent diabetic complications. However, few therapies address the etiology of neurodegeneration in the peripheral nervous systems of diabetic patients. Several metabolic mechanisms have been proposed as etiologies of this polyneuropathy. In this study, we revisited one of those mechanisms, the polyol pathway, and investigated the curative effects of a novel strong aldose reductase inhibitor, ranirestat, in streptozotocin-induced diabetic rats with preexisting polyneuropathy. Twelve weeks after the onset of diabetes, rats which had an established polyneuropathy were treated once daily with a placebo, ranirestat, or epalrestat, over 6 weeks. Before and after the treatment, nerve conduction velocities and thermal perception threshold of hindlimbs were examined. After the treatment, intraepidermal fiber density was evaluated. As an ex vivo assay, murine dorsal root ganglion cells were dispersed and cultured with or without 1 μmol/l ranirestat for 48 hours. After the culture, neurite outgrowth was quantified using immunological staining. Sensory nerve conduction velocity increased in diabetic rats treated with ranirestat (43.3±3.6 m/s) compared with rats treated with placebo (39.8±2.3). Motor nerve conduction velocity also increased in the ranirestat group (45.6±3.9) compared with the placebo group (38.9±3.5). The foot withdrawal latency to noxious heating was improved in the ranirestat group (17.7±0.6 seconds) compared with the placebo group (20.6±0.6). The decrease in the intraepidermal fiber density was significant in the diabetic placebo group (21.6±1.7/mm) but not significant in the diabetic ranirestat group (26.2±1.2) compared with the nondiabetic placebo group (30.3±1.5). Neurite outgrowth was promoted in the neurons supplemented with ranirestat (control 1446±147 μm/neuron, ranirestat 2175±149). Ranirestat improved the peripheral nervous dysfunctions in rats with advanced diabetic polyneuropathy. Ranirestat could have potential for regeneration in the peripheral nervous system of diabetic rats.


1998 ◽  
Vol 244 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Noriaki Kato ◽  
Mitsuhiro Makino ◽  
Kuniharu Mizuno ◽  
Tsunemasa Suzuki ◽  
Masaomi Shindo

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Lawrence Coppey ◽  
Bao Lu ◽  
Craig Gerard ◽  
Mark A. Yorek

We have demonstrated that treating diet-induced obese (DIO) mice with the vasopeptidase inhibitor ilepatril improved neural function. Vasopeptidase inhibitors block angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity. We propose that increased activity of ACE and NEP contributes to pathophysiology of DIO. To address this issue C57Bl/6J mice or mice deficient in NEP were fed a high-fat diet and treated with ilepatril, enalapril, ACE inhibitor, or candoxatril, NEP inhibitor, using both prevention and intervention protocols. Endpoints included glucose utilization and neural function determination. In the prevention study glucose tolerance was impaired in DIO C57Bl/6J mice and improved with ilepatril or enalapril. Sensory nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density were impaired in DIO C57Bl/6J mice and improved with ilepatril or candoxatril. In the intervention study only enalapril improved glucose tolerance. Sensory nerve conduction velocity and intraepidermal nerve fiber density were improved by all three treatments, whereas thermal nociception was improved by ilepatril or candoxatril. In NEP-deficient mice DIO impaired glucose utilization and this was improved with enalapril. Nerve function was not impaired by DIO in NEP-deficient mice. These studies suggest that ACE and NEP play a role in pathophysiology associated with DIO.


Author(s):  
Riccardo Marvulli ◽  
Giancarlo Ianieri ◽  
Grazia Devenuto ◽  
Marta Falcicchio ◽  
Giulia A. Gallo ◽  
...  

Background and Objective: Carpal tunnel syndrome (CTS) is the most common form of nerve entrapment. Clinically, various signs and symptoms compare due to overexposure to mechanical vibrations transmitted to the wrist bones and cartilage, resulting in compression of the sensory and motor nerve fibers of median nerve. Early symptoms include nocturnal paresthesia and electromyography reveals reduced sensory nerve conduction velocity. Aim of this study was to evaluate the efficacy of a dietary integrator composed of acetyl-L-carnitine, α-lipoic acid,quercetin, bromelain, pantothenic acid, C and B1 and B2 and B6 and B12 vitamins in patients with early (minimal) carpal tunnel syndrome. Methods: 36 patients (28 female and 8 male) with early CTS characterized by sensory nerve demyelination and inflammation of the transverse carpal ligament. Patients were divided into two groups, group A (18 patients received physical therapy) and group B (18 patients, received physical therapy and an oral integrator). Clinical (sleep quality questionnaire to measure severity of paresthesia) and neurophysiological assessment (Sensory Nerve Conduction Velocity) performed at baseline, and then at 30 and 60 days after treatment. Results: Sleep quality and Sensory Nerve Conduction Velocity data analysis show improvement in both groups at 30 and 60 days, with statistically difference between them in both time of analysis. Conclusions: In the early CTS, with sensory fibers damage, use of dietary integrator, such as Micronil Dol®, composed composed of acetyl-L-carnitine, α-lipoic acid,quercetin, bromelain, pantothenic acid, C and B1 and B2 and B6 and B12 vitamins can be effective in quick recovery of median nerve sensory.


2021 ◽  
Vol 9 (1) ◽  
pp. e001698
Author(s):  
Haifa Maalmi ◽  
Kristiaan Wouters ◽  
Hans H C M Savelberg ◽  
Jeroen H P M van der Velde ◽  
Jos P H Reulen ◽  
...  

IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.


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