• Kidney Research and Clinical Practice
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• v.35 no.2
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• Microbiology and Biotechnology Letters
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• v.18 no.5
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• pp.471-475
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• 1990

A thermostable adenylate kinase isolated from the sonic extracts of Thermus caldophilus cells revealed higher substrate-specificity to the nucleoside monophosphate than to the nucleoside triphosphate. A $P', P^5$-di(adenosine-5') pentaphosphate was acted as a competitive inhibitor to the various substrates. Various divalent cations were activated the enzyme activity following orders: $Mg^{2+}, Ca^{2+}, Mn^{2+}, Ba^[2+}, $ and $Fe^{2+}$-. The enzyme activity was not affected by the sulfurhydryl reagent, p-chloromeric uribenzoic acid and activated by addition of the sodium chloride or phosphoenol pyruvate to the reaction mixture.

• The Korean Journal of Physiology
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• v.26 no.1
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• pp.15-25
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• 1992

In order to elucidate the properties of the background current whole cell patch clamp studies were performed in rabbit ventricular cells. Ramp pulses of ${\pm}80\;mV$ from holding potential of 40 mV(or 20 mV) at the speed of 0.8 V/sec were given every 30 sec(or 10 sec) and current-voltage diagrams(I-V curve) were obtained. For the activation of the background current isoprenaline, adenosine 3',5'-cyclic monophosphate(dBcAMP), guanosine 3',5'-cyclic monophosphate(cGMP), and $N^6$-2'-o-dibutyryladenosine 3',5'-cyclic monophosphate(dBcAMP) were applied after all known current systems were blocked with 2mM Ba, 1 mM Cd ,5 mM Ni, 10 ${\mu}M$ diltiazem, 10 ${\mu}m$ ouabain, and 20 mM tetraethylammonium(TEA). The conductance of background current in control was $0.65{\pm}0.69$ nS at 0 mV, its I-V curves was almost linear and reversed near 50 mV. When there was no taurine in pipette solution, isoprenaline hardly activated the background current but when taurine existed in pipette solution, isoprenaline activated the larger background current. Cyclic AMP or cyclic GMP alone had little effect on the activation of the background current, while cGMP potentiated cGMP effect. When the background current was activated with cGMP and cAMP, isoprenaline could not further increased the background current. The background current activated by isoprenaline depended on extracellular $Cl^-$ concentration and its reversal potential was shifted according to chloride equilibrium potential. The change of extracellular $Na+$ concentration had little effect on reversal potential of the background current activated by isoprenaline.

• Food Science of Animal Resources
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• v.43 no.5
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• pp.805-825
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• 2023

This experiment aims to investigate the impact of probiotic feed on growth performance, carcass traits, plasma lipid biochemical parameters, intramuscular fat and triglyceride content, fatty acid composition, mRNA expression levels of genes related to lipid metabolism, and the activity of the enzyme in Sunit sheep. In this experiment, 12 of 96 randomly selected Sunit sheep were assigned to receive the basic diet or the basic diet supplemented with probiotics. The results showed that supplementation with probiotics significantly increased the loin eye area, and decreased plasma triglycerides and free fatty acids, increasing the content of intramuscular fat and triglycerides in the muscle and improving the composition of the fatty acids. The inclusion of probiotics in the diet reduced the expression of adenosine 5'-monophosphate-activated protein kinase alpha 2 (AMPKα2) mRNA and carnitine palmitoyltransferase 1B (CPT1B) mRNA, while increasing the expression of acetyl-CoA carboxylase alpha (ACCα) mRNA, sterol regulatory element-binding protein-1c (SREBP-1c) mRNA, fatty acid synthase mRNA, and stearoyl-CoA desaturase 1 mRNA. The results of this study indicate that supplementation with probiotics can regulate fat deposition and improves the composition of fatty acids in Sunit sheep through the signaling pathways AMPK-ACC-CPT1B and AMPK-SREBP-1c. This regulatory mechanism leads to an increase in intramuscular fat content, a restructuring of muscle composition of the fatty acids, and an enhancement of the nutritional value of meat. These findings contribute to a better understanding of the food science of animal resources and provide valuable references for the production of meat of higher nutritional value.

• International Journal of Molecular Medicine
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• v.45 no.2
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• pp.589-596
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• 2020

Acer okamotoanum is reported to have various antioxidant, anti-inflammatory and beneficial immune system effects. The anti-adipocyte differentiation effects and mechanisms of the ethyl acetate (EtOAc) fraction of an A. okamotoanum extraction was investigated in 3T3-L1 adipocyte cells. Treatment with differentiation inducers increased the level of triglycerides (TGs) in 3T3-L1 adipocyte cells compared with an untreated control. However, the EtOAc fraction of A. okamotoanum significantly decreased TGs. Treatment with 1, 2.5 and 5 ㎍/ml showed weak activity, but TG production was inhibited at 10 ㎍/ml compared with the control. In addition, A. okamotoanum caused a significant downregulation of proteins related to adipogenesis, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer binding protein-α, -β and peroxisome proliferator-activated receptor-γ, compared with the untreated control. Furthermore, A. okamotoanum significantly upregulated lipolysis related protein, hormone-sensitive lipase and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Therefore, these results indicate that A. okamotoanum suppressed adipogenesis and increased lipolysis and the activation of AMPK, suggesting a protective role in adipocyte differentiation.

• BMB Reports
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• v.40 no.5
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• pp.678-683
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• 2007

Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

• Molecules and Cells
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• v.43 no.1
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• pp.58-65
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• 2020

Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.

• Biomedical Science Letters
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• v.27 no.4
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• pp.270-276
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• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.641-654
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• 2023

Purpose: Sour cherry (Prunus cerasus L.) contains abounding phytochemicals, such as polyphenols and anthocyanins, and has antioxidative effects. Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator in enhancing the lipid metabolism. This study hypothesized that the intake of sour cherry affects AMPK signaling. Therefore, this study examined whether sour cherry regulates AMPK to balance the hepatic lipid metabolism and exert ameliorating effects. Methods: Male C57BL/6J mice had obesity induced with a 45% fat diet. The mice were divided into four groups: control (CON), high-fat diet (HFD), low percentage sour cherry powder (LSC), and high percentage sour cherry powder (HSC). The mice in the sour cherry groups were fed 1% sour cherry or 5% sour cherry in their respective diets for 12 weeks. Results: The body weight, visceral fat weight, and lipid droplet size significantly decreased in the treatment groups. The serum and hepatic triglyceride and total cholesterol levels improved significantly in the HSC group. The low-density lipoprotein cholesterol levels were also reduced significantly, whereas the high-density lipoprotein cholesterol levels were increased significantly in both treatment groups. The sterol regulator binding protein-1c and fatty acid synthase expression levels as fatty acid synthesis-related enzymes were significantly lower in the treatment groups than in the high-fat diet group. Furthermore, the adipose triglyceride lipase and hormone-sensitive lipase expression levels as lipolytic enzyme activity and AMPK/acetyl-CoA carboxylase/carnitine palmitoyltransferase-1 as fatty acid β-oxidation-related pathway were upregulated significantly in both sour cherry groups. Conclusions: These results show that sour cherry intake improves hepatic lipid synthesis and chronic diseases by activating AMPK signaling. Therefore, this study suggests that phytochemical-rich sour cherry can be developed as a healthy functional food.

• Journal of Korean Medicine for Obesity Research
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• v.15 no.2
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• pp.131-136
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• 2015

Objectives: The prevalence of obesity and metabolic syndrome is increasing worldwide. Regulation of cellular energy metabolis has the potential to be manipulated therapeutically to serve as a target for obesity and insulin resistance. Skeletal muscle is regarded as a target for regulation of energy metabolism and insulin resistance. In this study, the authors investigated the regulatory effect of (Cinnamomum cassia Blume, CCB), Aconitum carmichaeli Debx (ACD), and Benth (Pueraria lobata Benth, PLB) on energy and glucose metabolism in C2C12 myotubes. Methods: The water extracts of CCB, ACD, and PLB (0.5 mg/ml) were treated in differentiated C2C12 myotubes. The expressions of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK were detected with western blotting. Glucose metabolism was investigated with glucose uptake assay and glucose consumption assay, total adenosine triphosphate (ATP) content was also analyzed. Results: CCB, ACD, and PLB activated the phophorylation of AMPK, they also increased the glucose metabolism and total ATP contents in C2C12 myotubes. Conclusions: This study suggests that CCB, ACD, and PLB have the potential to increase energy and glucose metabolism in skeletal muscle.