AMPK Activity: A Primary Target for Diabetes Prevention with Therapeutic Phytochemicals

Chung, Min‐Yu; Choi, Hyo‐Kyoung

doi:10.3390/nu13114050

Cited by 25 publications

(11 citation statements)

References 88 publications

(182 reference statements)

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“…In this research, we looked into the impacts of PSC-FEs on two principal pathways involved in insulin resistance, i.e., AMPK and AKT [ 4 , 19 ] and also on expression levels of INSR [ 20 ], GLUT1, and GLUT4 [ 21 ], as major regulators of glucose hemostasis.…”

Section: Discussionmentioning

confidence: 99%

Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

Esfahani

Tarighi

Dianat

et al. 2023

BMC Complement Med Ther

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Background Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. Methods The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. Results We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. Conclusions Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.

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Section: Discussionmentioning

confidence: 99%

Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

Esfahani

Tarighi

Dianat

et al. 2023

BMC Complement Med Ther

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“…Within this view, the hypolipidemic effect of AMPK can be attributed to its phosphorylation capabilities which result in the inhibition of lipogenesis and the stimulation of the oxidation of FAs by suppressing SREBP1, FA-synthesis genes, and ACC [ 66 ]. On the other hand, AMPK can reduce fasting glucose levels and enhance IR by stimulating peripheral glucose clearance and increasing the membranous translocation of GLUT2/4, and lowering membrane cholesterol [ 13 , 67 , 68 ]. Furthermore, the activation of AMPK by metformin, AICAR, and a-769662 has been shown to suppress hepatic gluconeogenesis and glucose production by reducing the expression and activation of key glucose-synthesis enzymes such as PEPCK and G6Pase activity in STZ-diabetic mice [ 66 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…The adenosine monophosphate-activated protein kinase (AMPK) is the major energy sensor molecule in the majority of cells that can regulate substrate metabolism and stimulate ATP production and cell survival in response to high AMP or ADP/ATP ratio [ 12 ]. Even though AMPK is a novel regulator of cellular energy sensors, it functions as an important therapeutic target for obesity, metabolic disease, and DM by acting through defined metabolic pathways in the liver, adipose tissue, and muscles [ 13 ]. These mechanisms include inhibiting gluconeogenesis, stimulating glucose intake and FA oxidation, and suppressing lipogenesis [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK

et al. 2023

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This study examined the protective effect of 11-keto-β-boswellic acid (AKBA) against streptozotocin (STZ)-induced diabetic cardiomyopathy (DC) in rats and examined the possible mechanisms of action. Male rats were divided into 5 groups (n = 8/each): (1) control, AKBA (10 mg/kg, orally), STZ (65 mg/kg, i.p.), STZ + AKBA (10 mg/kg, orally), and STZ + AKBA + compound C (CC/an AMPK inhibitor, 0.2 mg/kg, i.p.). AKBA improved the structure and the systolic and diastolic functions of the left ventricles (LVs) of STZ rats. It also attenuated the increase in plasma glucose, plasma insulin, and serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), and free fatty acids (FFAs) in these diabetic rats. AKBA stimulated the ventricular activities of phosphofructokinase (PFK), pyruvate dehydrogenase (PDH), and acetyl CoA carboxylase (ACC); increased levels of malonyl CoA; and reduced levels of carnitine palmitoyltransferase I (CPT1), indicating improvement in glucose and FA oxidation. It also reduced levels of malondialdehyde (MDA); increased mitochondria efficiency and ATP production; stimulated mRNA, total, and nuclear levels of Nrf2; increased levels of glutathione (GSH), heme oxygenase (HO-1), superoxide dismutase (SOD), and catalase (CAT); but reduced the expression and nuclear translocation of NF-κB and levels of tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These effects were concomitant with increased activities of AMPK in the LVs of the control and STZ-diabetic rats. Treatment with CC abolished all these protective effects of AKBA. In conclusion, AKBA protects against DC in rats, mainly by activating the AMPK-dependent control of insulin release, cardiac metabolism, and antioxidant and anti-inflammatory effects.

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“…Diabetes mellitus (DM) is a chronic metabolic disorder chiefly characterized by hyperglycemia, and the incidence of DM is increasing worldwide [ 1 ]. Diabetic nephropathy (DN), the most common microvascular complication of DM, is primarily featured by albuminuria and progressive loss of kidney function [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

Cheng

Zhang

et al. 2023

Renal Failure

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Objectives: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus. This study investigated the mechanism of triptolide (TP) in podocyte injury in DN. Methods: DN mouse models were established by feeding with a high-fat diet and injecting with streptozocin and MPC5 podocyte injury models were induced by high-glucose (HG), followed by TP treatment. Fasting blood glucose and renal function indicators, such as 24 h urine albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and kidney/body weight ratio of mice were examined. H&E and TUNEL staining were performed for evaluating pathological changes and apoptosis in renal tissue. The podocyte markers, reactive oxygen species (ROS), oxidative stress (OS), serum inflammatory cytokines, nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway-related proteins, and pyroptosis were detected by Western blotting and corresponding kits. MPC5 cell viability and pyroptosis were evaluated by MTT and Hoechst 33342/PI double-fluorescence staining. Nrf2 inhibitor ML385 was used to verify the regulation of TP on Nrf2. Results: TP improved renal function and histopathological injury of DN mice, alleviated podocytes injury, reduced OS and ROS by activating the Nrf2/heme oxygenase-1 (HO-1) pathway, and weakened pyroptosis by inhibiting the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome pathway. In vitro experiments further verified the inhibition of TP on OS and pyroptosis by mediating the Nrf2/HO-1 and NLRP3 inflammasome pathways. Inhibition of Nrf2 reversed the protective effect of TP on MPC5 cells. Conclusions: Overall, TP alleviated podocyte injury in DN by inhibiting OS and pyroptosis via Nrf2/ROS/NLRP3 axis.

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AMPK Activity: A Primary Target for Diabetes Prevention with Therapeutic Phytochemicals

Cited by 25 publications

References 88 publications

Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells

The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK

Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

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