scholarly journals Antidiabetic Flavonoids from Fruits of Morus alba Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 526
Author(s):  
Sung Ho Lim ◽  
Jae Sik Yu ◽  
Ho Seon Lee ◽  
Chang-Ik Choi ◽  
Ki Hyun Kim
Keyword(s):  
Side Effects ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
High Performance ◽  
Ethanolic Extract ◽  
Morus Alba ◽  
Phytochemical Analysis ◽  
Ampk Signaling ◽  
Amp Activated Protein Kinase

Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their underlying mechanisms of action. Consequently, in this study, the fruits of M. alba were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of M. alba fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-O-β-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in M. alba fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.

scholarly journals P2-316: Disturbance in AMP-activated protein kinase (AMPK) signaling pathway in Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. S406-S406
Author(s):  
Hyoung-Gon Lee ◽  
Hyun-Pil Lee ◽  
Wataru Kudo ◽  
Xiongwei Zhu ◽  
George Perry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Ampk Signaling ◽  
Amp Activated Protein Kinase

scholarly journals Fridamycin A, a Microbial Natural Product, Stimulates Glucose Uptake without Inducing Adipogenesis

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 765 ◽  
Author(s):  
Sun-Young Yoon ◽  
Seoung Rak Lee ◽  
Ji Young Hwang ◽  
René Benndorf ◽  
Christine Beemelmanns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Polyketide Synthase ◽  
Term Treatment ◽  
Ampk Signaling ◽  
Microbial Product ◽  
Long Term Treatment

Type 2 diabetes is a complex, heterogeneous, and polygenic disease. Currently, available drugs for treating type 2 diabetes predominantly include sulfonylureas, α-glucosidase inhibitors, and biguanides. However, long-term treatment with these therapeutic drugs is often accompanied by undesirable side effects, which have driven interest in the development of more effective and safer antidiabetic agents. To address the urgent need for new chemical solutions, we focused on the analysis of structurally novel and/or biologically new metabolites produced by insect-associated microbes as they have recently been recognized as a rich source of natural products. Comparative LC/MS-based analysis of Actinomadura sp. RB99, isolated from a fungus-growing termite, led to the identification of the type II polyketide synthase-derived fridamycin A. The structure of fridamycin A was confirmed by 1H NMR data and LC/MS analysis. The natural microbial product, fridamycin A, was examined for its antidiabetic properties in 3T3-L1 adipocytes, which demonstrated that fridamycin A induced glucose uptake in 3T3-L1 cells by activating the AMP-activated protein kinase (AMPK) signaling pathway but did not affect adipocyte differentiation, suggesting that the glucose uptake took place through activation of the AMPK signaling pathway without inducing adipogenesis. Our results suggest that fridamycin A has potential to induce fewer side effects such as weight gain compared to rosiglitazone, a commonly used antidiabetic drug, and that fridamycin A could be a novel potential therapeutic candidate for the management of type 2 diabetes.

A-769662 potentiates the effect of other AMP-activated protein kinase activators on cardiac glucose uptake

2014 ◽  
Vol 306 (12) ◽  
pp. H1619-H1630 ◽  
Author(s):  
Aurélie D. Timmermans ◽  
Magali Balteau ◽  
Roselle Gélinas ◽  
Edith Renguet ◽  
Audrey Ginion ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Ampk Activation ◽  
Perfused Heart ◽  
Ampk Signaling ◽  
Metabolic Outcome ◽  
Amp Activated Protein Kinase ◽  
The Impact

AMP-activated protein kinase (AMPK), a key cellular sensor of energy, regulates metabolic homeostasis and plays a protective role in the ischemic or diabetic heart. Stimulation of cardiac glucose uptake contributes to this AMPK-mediated protection. The small-molecule AMPK activator A-769662, which binds and directly activates AMPK, has recently been characterized. A-769662-dependent AMPK activation protects the heart against an ischemia-reperfusion episode but is unable to stimulate skeletal muscle glucose uptake. Here, we tried to reconcile these conflicting findings by investigating the impact of A-769662 on cardiac AMPK signaling and glucose uptake. We showed that A-769662 promoted AMPK activation, resulting in the phosphorylation of several downstream targets, but was incapable of stimulating glucose uptake in cultured cardiomyocytes and the perfused heart. The lack of glucose uptake stimulation can be explained by A-769662's narrow specificity, since it selectively activates cardiac AMPK heterotrimeric complexes containing α2/β1-subunits, the others being presumably required for this metabolic outcome. However, when combined with classical AMPK activators, such as metformin, phenformin, oligomycin, or hypoxia, which impact AMPK heterotrimers more broadly via elevation of cellular AMP levels, A-769662 induced more profound AMPK phosphorylation and subsequent glucose uptake stimulation. The synergistic effect of A-769662 under such ischemia-mimetic conditions protected cardiomyocytes against ROS production and cell death. In conclusion, despite the fact that A-769662 activates AMPK, it alone does not significantly stimulate glucose uptake. However, strikingly, its ability of potentiating the action on other AMPK activators makes it a potentially useful participant in the protective role of AMPK in the heart.

scholarly journals The effects of evodiamine on serum total cholesterol and triglyceride levels are associated with the activation of the AMPK signaling pathway in rats with hyperlipemia

2016 ◽  
Vol 68 (3) ◽  
pp. 561-566 ◽  
Author(s):  
Hui Yu ◽  
Hai Hu ◽  
Wuzhuang Gong ◽  
Yang Li ◽  
Zhanli Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Total Cholesterol ◽  
Signaling Pathway ◽  
Biological Activities ◽  
Indole Alkaloid ◽  
Serum Levels ◽  
Serum Total Cholesterol ◽  
Ampk Signaling ◽  
Naturally Occurring ◽  
Amp Activated Protein Kinase

Evodiamine, a naturally occurring indole alkaloid, has been reported to have numerous biological activities, including antitumor, antimicrobial and anti-inflammatory effects. Previous studies also suggest that evodiamine prevents obesity. In this study, we confirmed that evodiamine lowered the levels of serum total cholesterol (TC) and triglycerides(TG) in rats with hyperlipemia. Furthermore, our findings suggest that the activation of the AMP-activated protein kinase (AMPK) pathway might contribute in part to the effect of evodiamine on the serum levels of TC and TG.

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