Polyphenols targeting diabetes via the AMP-activated protein kinase pathway; future approach to drug discovery

Momtaz, Saeideh; Maghsoudi, Armin Salek; Abdolghaffari, Amir Hossein; Jasemi, Eghbal; Rezazadeh, Shamsali; Hassani, Shokoufeh; Ziaee, Mojtaba; Abdollahi, Mohammad; Behzad, Sahar; Nabavi, Seyed Mohammad

doi:10.1080/10408363.2019.1648376

Cited by 37 publications

(25 citation statements)

References 155 publications

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“…High anthocyanin intake induced a significant reduction in peripheral insulin resistance detected in females aged 18–76 years [ 103 ]. The increase in plasma insulin level and the improvement of glycemic control in type 2 diabetic adults were reported after daily consumption of Cornus mas extract for 6 weeks [ 104 , 105 ].…”

Section: Resultsmentioning

confidence: 99%

“…The in vitro studies showed that the suppression of gut glucose absorption is the major mechanism of anthocyanin anti-diabetic effect through inhibition of α-glucosidase and α-amylase enzymes. The substitution of glucose or galactose enhances the enzyme inhibition activity at the 3-O position or by acylation with ferulic or caffeic acid derivatives [ 103 , 105 ].…”

Section: Resultsmentioning

confidence: 99%

“…These forms can also offer an extra advantage of controlling the release of the substance. More studies must decide the appropriate consumption and the most effective type as antidiabetic [ 99 , 102 , 103 , 106 ].…”

Section: Resultsmentioning

confidence: 99%

“…Enhancement of insulin failure to trigger signal transduction in tissues and the restoring of insulin sensitivity by polyphenols were reported to be mediated by activating the AMPK pathway in many in vivo and in vitro studies. Recently, AMPK was proposed as a major drug target to treat diabetes [ 20 , 103 ]. Its activation prompted upregulation of GLUT-4 and enhancement of glucose uptake, reduction in hepatic glucose production and increase fatty acid oxidation.…”

Section: Discussionmentioning

confidence: 99%

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Plants Secondary Metabolites as Blood Glucose-Lowering Molecules

2021

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Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants’ secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plants Secondary Metabolites as Blood Glucose-Lowering Molecules

2021

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“…Due to the essential role of AMPK on glucose and lipid metabolism, the exploration of molecules that can activate AMPK is an emerging field both in pharmacology and nutrition (Grahame Hardie, 2016; Hao et al , 2021; Olivier et al , 2018). Several bioactive compound such as phenolic compound and polyphenols have been reported to activate AMPK and ameliorate glucose uptake in insulin resistance condition (Huang et al , 2015; Vazirian et al , 2018; Momtaz et al , 2019). Gatot contains phenolic compound derived from filamentous fungi such as Rhizopus oryzae and Acremonium charticola (Sugiharto et al , 2016).…”

Section: Discussionmentioning

confidence: 99%

Effect of fermented cassava tuber on the gene expression of PI3K/Akt signaling and AMPK pathway in STZ-NA-induced diabetic rats

Kusuma

Puspaningtyas

Sari

2022

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Purpose The downstream insulin signaling, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway, is an important step for skeletal glucose disposal through the translocation of glucose transporter (GLUT)-4. In addition, the master of energy regulator adenosine monophosphate-activated kinase (AMPK) is also involved in GLUT-4 translocation, independent from the PI3K/Akt pathway. Fermented cassava tuber or gatot is a traditional food from Indonesia with antihyperglycemic properties. However, the molecular mechanism leading to this effect is unclear. Therefore, this paper aims to evaluate whether the antidiabetic activity of gatot is through PI3K/Akt dependent or AMPK pathway. Design/methodology/approach Diabetes mellitus was induced in 20 male Wistar rats by intraperitoneal injection of 65 mg/kg body weight streptozotocin and 230 mg/kg body weight nicotinamide. Diabetic rats were randomly allocated into four groups; negative control, positive control (metformin 100 mg/kg body weight), fermented cassava diet replacing 50% of carbohydrate (FC-50) and 100% of carbohydrate (FC-100) in the diet. Serum glucose, insulin and lipid profile were analyzed before and after four weeks of intervention. Genes expression of PI3K subunit alpha, PI3K subunit beta, PI3K regulatory subunit, Akt and AMPK were analyzed using real time polymerase chain reaction (PCR). GLUT-4 protein expression was performed using immunohistochemistry. Findings There is a significant difference (p = 0.000) in serum glucose, insulin, total cholesterol, triglyceride, high density lipoprotein (HDL)-cholesterol and LDL-cholesterol between groups. Skeletal AMPK gene expression was higher and significantly different between FC-100 (p = 0.006) and healthy control groups. No significant difference was observed in the messenger ribonucleic acid (mRNA) expression of the PI3K/Akt pathway among groups. GLUT-4 expression was highly expressed in a positive control group followed by FC-100. Research limitations/implications This paper did not characterize the bioactive component that is responsible for increasing mRNA expression of AMPK. This paper also did not analyze the phosphorylation of PI3K/Akt and AMPK that are important in activating the protein. Originality/value To the best of the authors’ knowledge, this is the first study that showed the antidiabetic activity of traditional fermented food is through AMPK-dependent activity.

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