Is metformin a possible treatment for diabetic neuropathy?

Wei, Juechun; Wei, Yanling; Huang, Meiyan; Wang, Peng; Jia, Shushan

doi:10.1111/1753-0407.13310

Cited by 13 publications

(8 citation statements)

References 116 publications

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“…Metformin has multiple mechanisms of action, including AMPK activation, inhibition of mitochondrial respiration, increasing insulin sensitivity, and antagonizing the effects of glucagon [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Sildenafil–Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice

Pușcașu,

Ungurianu,

Șeremet

et al. 2023

Medicina

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Background and objectives: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. Methods: The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. Results: In both the hot-plate and tail withdrawal test, all sildenafil–metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil–metformin combinations. Conclusions: The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil–metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS.

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Section: Discussionmentioning

confidence: 99%

The Influence of Sildenafil–Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice

Pușcașu,

Ungurianu,

Șeremet

et al. 2023

Medicina

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“…GLP-1 also enhances cAMP production to facilitate a PKA-induced closure of KATP channels (47). Whether or not metformin or GLP-1 agonists directly or indirectly influences ion channel excitability, and therefore influences incidence of chronic pain, particularly from diabetes is up for debate (66)(67)(68). According to a recent cohort study, patients with diabetes who taking opioids were at increased risk of early mortality compared to diabetic and non-diabetic participants who did not use opiates and non-diabetics using opiates (69).…”

Section: Discussionmentioning

confidence: 99%

Loss of ATP-sensitive channel expression and function decreases opioid sensitivity in a mouse model of type 2 diabetes

Fisher,

Johnson,

Moore

et al. 2023

Preprint

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During diabetes, β-cell dysfunction due to loss of potassium channels sensitive to ATP, known as KATPchannels occurs progressively over time contributing to hyperglycemia. KATPchannels are additionally present in the central and peripheral nervous systems and are downstream targets of opioid receptor signaling. The aim of this study is to investigate if KATPchannel expression or activity in the nervous system changes in diabetic mice and if morphine antinociception changes in mice fed a high fat diet (HFD) for 16 weeks compared to controls. Mechanical thresholds were also monitored before and after administration of glyburide or nateglinide, KATPchannel antagonists, for four weeks. HFD mice have decreased antinociception to systemic morphine, which is exacerbated after systemic treatment with glyburide or nateglinide. HFD mice also have lower rotarod scores, decreased mobility in an open field test, and lower burrowing behavior compared to their control diet counterparts, which is unaffected by KATPchannel antagonist delivery. Expression of KATPchannel subunits, Kcnj11 (Kir6.2) and Abcc8 (SUR1), were decreased in the peripheral and central nervous system in HFD mice, which is significantly correlated with baseline paw withdrawal thresholds. Upregulation of SUR1 through an adenovirus delivered intrathecally increased morphine antinociception in HFD mice, whereas Kir6.2 upregulation improved morphine antinociception only marginally. Perspective: This article presents the potential link between KATPchannel function and neuropathy during diabetes. There is a need for increased knowledge in how diabetes affects structural and molecular changes in the nervous system to lead to the progression of chronic pain and sensory issues.

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“…151 In addition, metformin, an insulin sensitiser widely used in the treatment of NAFLD, IR and type 2 diabetes, has been found to inhibit the absorption of B12. 152 Mahabir S et al found the serum FA in the overweight postmenopausal women was lower than healthy individuals despite the adequate intake of FA. 153 Therefore, the supplementation of FA and B12 in addition to the application of such patient may be beneficial to the NAFLD, and the effect of dietary structure changes or probiotic supplementation may be better than that of oral FA supplementation alone, but needed further verification studies.…”

Section: Conclusion and Future Considerationsmentioning

confidence: 98%

“…In addition, metformin, an insulin sensitiser widely used in the treatment of NAFLD, IR and type 2 diabetes, has been found to inhibit the absorption of B12 152 . Mahabir S et al.…”

Section: Conclusion and Future Considerationsmentioning

confidence: 99%

The relationship between folic acid and nonalcoholic fatty liver disease

Xu,

Yang,

Zhu

et al. 2024

Clinical and Translational Dis

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In recent years, the incidence of non‐alcoholic fatty liver disease (NAFLD) has been increasing, which has become an explosive interest because of the growing impact on world health. NAFLD is the hepatic manifestation of systemic metabolic syndrome (MS), and the umbrella term that comprises a continuum of liver conditions, from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and hepatocellular carcinoma (HCC). currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folic acid (FA) was one of a water‐soluble B vitamins, entirely absorbed from the diet. Numbers of clinical studies have confirmed that patients with NAFLD and insulin resistance are often accompanied by abnormal FA. We investigated the potential effects of FA on NAFLD through the metabolic pathways, DNA synthesis and methylation, oxidative stress in liver and intestinal flora. In addition, FA has an effect on HCC or other cancer. Therefore, FA might be a safe and economical potential treatment method for NAFLD.

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Is metformin a possible treatment for diabetic neuropathy?

Cited by 13 publications

References 116 publications

The Influence of Sildenafil–Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice

The Influence of Sildenafil–Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice

Loss of ATP-sensitive channel expression and function decreases opioid sensitivity in a mouse model of type 2 diabetes

The relationship between folic acid and nonalcoholic fatty liver disease

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