Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs

Chung, Ming-Min; Nicol, Christopher J.B.; Cheng, Yi-Chuan; Lin, Kuan‐Hung; Chen, Yen‐Lin; Pei, Dee; Lin, Chien‐Hung; Shih, Yi-Nuo; Yen, Chia‐Hui; Chen, Shiang-Jiuun; Huang, Rong‐Nan; Chiang, Ming‐Chang

doi:10.1016/j.yexcr.2017.01.017

Cited by 53 publications

(27 citation statements)

References 100 publications

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“…The anti-inflammatory actions of metformin have been reported in a variety of cell types. First, metformin has been reported to reduce the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, through inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in macrophages [10,11]. The cytokines mentioned here do not only function as final products of inflammation, but crosstalk with each other's signaling systems while mediating various skin inflammatory processes.…”

Section: Potential Molecular Mechanisms Of Action For Metforminmentioning

confidence: 99%

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

Chang

Choi

2020

IJMS

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Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

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Section: Potential Molecular Mechanisms Of Action For Metforminmentioning

confidence: 99%

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

Chang

Choi

2020

IJMS

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“…The IKK/NF-κB pathway promotes its own feedback to limit the response to IL-1β and TNF-α, notably by inducing the transcription of IκBα (56). Activation of AMPK may be another way to limit NF-κB signaling in response to these cytokines, indicated by several studies (57, 58). TNF-α-induced apoptosis is opposed by AMPK (59), which is in line with the role of IKK in promoting survival over apoptosis in response to TNF-α.…”

Section: Discussionmentioning

confidence: 99%

IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells

Antonia

Baldwin

2018

Sci. Signal.

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The 5' AMP-activated protein kinase (AMPK) is an energy sensor that is activated upon phosphorylation of Thr in its activation loop by the kinase LKB1, CAMKK2, or TAK1. TAK1-dependent AMPK phosphorylation of Thr is less well characterized than phosphorylation of this site by LKB1 or CAMKK2. An important target of TAK1 is IκB kinase (IKK), which controls the activation of the transcription factor NF-κB. We tested the hypothesis that IKK acted downstream of TAK1 to activate AMPK by phosphorylating Thr IKK was required for the phosphorylation of Thr in AMPK in response to treatment with the inflammatory cytokine IL-1β or TNF-α or upon TAK1 overexpression. In addition, IKK regulated basal AMPK Thr phosphorylation in several cancer cell types independently of TAK1, indicating that other modes of IKK activation could stimulate AMPK. We found that IKK directly phosphorylated AMPK at Thr independently of the tumor suppressor LKB1 or energy stress. Accordingly, in LKB1-deficient cells, IKK inhibition reduced AMPK Thr phosphorylation in response to the mitochondrial inhibitor phenformin. This response led to enhanced apoptosis and suggests that IKK inhibition in combination with phenformin could be used clinically to treat patients with LKB1-deficient cancers.

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“…Metformin protects the cardiovascular system from oxidative stress and inflammation via 5′‐adenosine monophosphate‐activated protein kinase‐dependent‐ and ‐independent pathways15, 16 and clinical trials supported an antiatherogenic effect of metformin 17. Metformin inhibits the formation of advanced glycation end products,18, 19 attenuates glucose‐induced endothelial dysfunction,20 and increases nitric oxide production and improves angiogenic functions 21…”

Section: Discussionmentioning

confidence: 99%

Metformin and Risk of Hypertension in Taiwanese Patients With Type 2 Diabetes Mellitus

Tseng

2018

JAHA

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BackgroundWhether metformin use may reduce hypertension risk has not been studied. This study investigated such possibility in patients with type 2 diabetes mellitus.Methods and ResultsNewly diagnosed patients with type 2 diabetes mellitus during 1999–2005 were enrolled from the reimbursement database of the Taiwan's National Health Insurance and followed to December 31, 2011. Hypertension was defined either by a diagnosis or by a diagnosis plus the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers and/or calcium channel blockers. Analyses were conducted in a propensity score matched‐pair cohort of 4810 ever users and 4810 never users. Cox proportional hazards regression model was used to estimate the hazard ratios. Results showed that when hypertension was defined by a diagnosis, 2261 never users and 1908 ever users developed hypertension. The overall hazard ratio was 0.724 (0.681–0.769) and the hazard ratios for the first (<2.0 months), second (2.0–13.0 months) and third (>13.0 months) tertiles of cumulative duration were 0.820 (0.745–0.903), 0.692 (0.634–0.756), and 0.687 (0.630–0.749), respectively. When cumulative duration of metformin therapy was treated as a continuous variable, the hazard ratio was 0.991 (0.989–0.994) for every 1‐month increment of metformin use. When hypertension was defined by a diagnosis plus the use of antihypertensive drugs, the overall hazard ratio was 0.831 (0.771–0.895), the hazard ratios for the respective tertiles were 0.868 (0.769–0.980), 0.852 (0.767–0.946), and 0.787 (0.709–0.874), and the hazard ratio was 0.994 (0.991–0.997) for every 1‐month increment of metformin use.ConclusionsA reduced risk of hypertension is observed in metformin users in a dose‐response pattern.

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Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs

Cited by 53 publications

References 100 publications

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders

IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells

Metformin and Risk of Hypertension in Taiwanese Patients With Type 2 Diabetes Mellitus

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