Diabetic neuropathy: therapies on the horizon

Mahmood, Danish; Singh, Bhulan Kumar; Akhtar, M. Humayoun

doi:10.1211/jpp.61.09.0002

Cited by 31 publications

(26 citation statements)

References 78 publications

(78 reference statements)

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“…Taken together, the findings give rise to future treatment possibilities including agents that directly support neurons and reparative processes after injury (39) or modalities with an effect on neuromodulation, such as peripheral pacing of visceral nerves (40). …”

Section: Discussionmentioning

confidence: 99%

Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

et al. 2013

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OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.RESULTSDiabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2–P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001).CONCLUSIONSThis study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.

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Section: Discussionmentioning

confidence: 99%

Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

et al. 2013

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“…Aldose reductase-mediated reduction of glucose to sorbitol is associated with consumption of NADPH, and since NADPH is required for regeneration of reduced glutathione (GSH), this directly contributes to oxidative stress. In addition, formation of fructose from sorbitol promotes glycation, depletes NADPH, and increases AGEs which all result in major redox imbalance (see Figure 2) [9, 10]. …”

Section: Pathogenesis Of Dn: Interaction Of Oxidative Stress With mentioning

confidence: 99%

“…Long-term inflammatory responses upregulate RAGE and stimulate nuclear factor kappa B (NF κ B). Collectively, the biochemical damage induced by AGEs results in diminished neurotrophic support, impaired nerve blood flow, disrupted neuronal integrity, and impaired repair mechanisms (Figure 2) [3, 10]. …”

Section: Pathogenesis Of Dn: Interaction Of Oxidative Stress With mentioning

confidence: 99%

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

Hosseini

Abdollahi

2013

Oxidative Medicine and Cellular Longevity

180

124

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Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

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“…Hyperglycemia is the major cause of diabetic complications, such as retinopathy, nephropathy, and neuropathy [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

Ferulsinaic Acid Modulates SOD, GSH, and Antioxidant Enzymes in Diabetic Kidney

Sayed

2012

Evidence-Based Complementary and Alternative Medicine

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The efficacy of Ferulsinaic acid (FA) to modulate the antioxidant enzymes and to reduce oxidative stress induced-diabetic nephropathy (DN) was studied. Rats were fed diets enriched with sucrose (50%, wt/wt), lard (30%, wt/wt), and cholesterol (2.5%, wt/wt) for 8 weeks to induce insulin resistance. After a DN model was induced by streptozotocin; 5, 50 and 500 mg/kg of FA were administrated by oral intragastric intubation for 12 weeks. In FA-treated diabetic rats, glucose, kidney/body weight ratio, creatinine, BUN, albuminurea, and creatinine clearance were significantly decreased compared with non treated diabetic rats. Diabetic rats showed decreased activities of SOD and GSH; increased concentrations of malondialdehyde and IL-6 in the serum and kidney, and increased levels of 8-hydroxy-2′-deoxyguanosine in urine and renal cortex. FA-treatment restored the altered parameters in a dose-dependent manner. The ultra morphologic abnormalities in the kidney of diabetic rats were markedly ameliorated by FA treatment. Furthermore, FA acid was found to attenuate chronic inflammation induced by both Carrageenan and dextran in rats. We conclude that FA confers protection against injuries in the kidneys of diabetic rats by increasing activities of antioxidant enzymes and inhibiting accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.

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Diabetic neuropathy: therapies on the horizon

Cited by 31 publications

References 78 publications

Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

Ferulsinaic Acid Modulates SOD, GSH, and Antioxidant Enzymes in Diabetic Kidney

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