Displaying publications 1 - 20 of 30 in total

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  1. Kanagasabapathy G, Chua KH, Malek SN, Vikineswary S, Kuppusamy UR
    Food Chem, 2014 Feb 15;145:198-204.
    PMID: 24128468 DOI: 10.1016/j.foodchem.2013.08.051
    Mushrooms have been used to treat various diseases for thousands of years. In the present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis, lipolysis and oxidative stress in 3T3-L1 cells were investigated. The β-glucan-rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells. This extract caused an increase in the expression of 5'-AMP-activated protein kinase subunit γ-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit γ-3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes, leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have contributed to the lipolytic and insulin-like activities observed in this study. These findings suggest that GE is a novel AMPK activator that may be valuable in the formulation of nutraceuticals and functional food for the prevention and treatment of diabetes mellitus.
    Matched MeSH terms: AMP-Activated Protein Kinases/physiology*
  2. Yap PG, Choi SB, Liong MT
    Appl Biochem Biotechnol, 2020 May;191(1):226-244.
    PMID: 32125649 DOI: 10.1007/s12010-020-03265-2
    This study aimed to evaluate the effect of probiotic administration on obese and ageing models. Sprague Dawley rats were subjected to high-fat diet (HFD) and injected with D-galactose to induce premature ageing. Upon 12 weeks of treatment, the faecal samples were collected and subjected to gas chromatography-mass spectrophotometry (GC-MS) analysis for metabolite detection. The sparse partial least squares discriminant analysis (sPLS-DA) showed a distinct clustering pattern of metabolite profile in the aged and obese rats administered with probiotics Lactobacillus plantarum DR7 and L. reuteri 8513d, particularly with a significantly higher concentration of allantoin. Molecular docking simulation showed that allantoin promoted the phosphorylation (activation) of adenosine monophosphate-activated kinase (AMPK) by lowering the substrate free energy of binding (FEB) and induced the formation of an additional hydrogen bond between Val184 and the substrate AMP. Allantoin also suppressed cholesterol biosynthesis by either inducing enzyme inhibition, occupying or blocking the putative binding site to result in non-spontaneous substrate binding, as in the cases of 3-hydroxy-methylglutaryl-coA reductase (HMGCR), mevalonate kinase (MVK) and lanosterol demethylase (LDM) where positive FEBs were reported. These results demonstrated the potential of allantoin to alleviate age-related hypercholesterolaemia by upregulating AMPK and downregulating cholesterol biosynthesis via the mevalonate pathway and Bloch pathway.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism*
  3. Zhou Z, Zhao J, de Cruz CR, Xu H, Wang L, Xu Q
    Fish Physiol Biochem, 2023 Oct;49(5):951-965.
    PMID: 37665506 DOI: 10.1007/s10695-023-01234-0
    The study investigated the alleviated effects of Alpha-ketoglutaric acid (AKG) on the intestinal health of mirror carp (Cyprinus carpio Songpu) caused by soy antigenic protein. The diets were formulated from fishmeal (CON), 50% soybean meal (SBM), the mixture of glycinin and β-conglycinin (11 + 7S) and adding 1% AKG in the 11 + 7S (AKG). Carp (~ 4 g) in triplicate (30 fish per tank) was fed to apparent satiation thrice a day for six weeks. Compared with CON, SBM treatment resulted in significantly poor growth performance (P  0.05). Gene expression of tumor necrosis factor (TNF-α) and interleukin-1 β (IL-1β) in proximal intestines (PI) and distal intestines (DI) were increased (P 
    Matched MeSH terms: AMP-Activated Protein Kinases
  4. Mahmood ND, Mamat SS, Kamisan FH, Yahya F, Kamarolzaman MF, Nasir N, et al.
    Biomed Res Int, 2014;2014:695678.
    PMID: 24868543 DOI: 10.1155/2014/695678
    Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P<0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  5. Teoh WY, Wahab NA, Sim KS
    Nucleosides Nucleotides Nucleic Acids, 2017 Apr 03;36(4):243-255.
    PMID: 28323520 DOI: 10.1080/15257770.2016.1268693
    This study aims to investigate the mechanisms associated with the antiproliferation effect of guanosine on human colon carcinoma HCT 116 cells. In this study, guanosine induced more drastic cell cycle arrest effect than cell death effect on HCT 116 cells. The cell cycle arrest effect of guanosine on HCT 116 cells appeared to be associated with the increased activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, p38 and JNK. The decrease of AMP-activated protein kinase (AMPK) activation and cyclin D1 expression was also involved. Thus, the antiproliferation of colon cancer cells of guanosine could be mediated by the disruption of MAPK and AMPK pathways.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism*
  6. Elhassan SAM, Candasamy M, Chan EWL, Bhattamisra SK
    Diabetes Metab Syndr, 2018 Nov;12(6):1109-1116.
    PMID: 29843994 DOI: 10.1016/j.dsx.2018.05.020
    BACKGROUND: Autophagy is a process devoted to degrade and recycle cellular components inside mammalian cells through lysosomal system. It plays a main function in the pathophysiology of several diseases. In type 2 diabetes, works demonstrated the dual functions of autophagy in diabetes biology. Studies had approved the role of autophagy in promoting different routes for movement of integral membrane proteins to the plasma membrane. But its role in regulation of GLUT4 trafficking has not been widely observed. In normal conditions, insulin promotes GLUT4 translocation from intracellular membrane compartments to the plasma membrane, while in type 2 diabetes defects occur in this translocation.

    METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.

    RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.

    CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.

    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  7. Odhaib KJ, Adeyemi KD, Sazili AQ
    Asian-Australas J Anim Sci, 2018 Aug;31(8):1345-1357.
    PMID: 29103284 DOI: 10.5713/ajas.17.0468
    Objective: This study examined the influence of dietary supplementation of Nigella sativa seeds, Rosmarinus officinalis leaves and their combination on carcass attributes, fatty acid (FA) composition, gene expression, lipid oxidation and physicochemical properties of longissimus dorsi (LD), semitendinosus (ST), and supraspinatus (SS) muscles in Dorper lambs.

    METHODS: Twenty-four Dorper lambs (18.68±0.6 kg, 4 to 5 months old) were randomly assigned to a concentrate mixture containing either, no supplement (control, T1), 1% Rosmarinus officinalis leaves (T2), 1% Nigella sativa seeds (T3), or 1% Rosmarinus officinalis leaves+1% Nigella sativa seeds (T4) on a dry matter basis. The lambs were fed the treatments with urea-treated rice straw for 90 days, slaughtered and the muscles were subjected to a 7 d postmortem chill storage.

    RESULTS: The T2 lambs had greater (p<0.05) slaughter and cold carcass weights than the control lambs. Dietary supplements did not affect (p>0.05) chill loss, dressing percentage, carcass composition, intramuscular fat and muscle pH in Dorper lambs. Meat from supplemented lambs had lower (p<0.05) cooking and drip losses, shear force, lightness, and lipid oxidation and greater (p<0.05) redness compared with the control meat. The impact of dietary supplements on muscle FA varied with muscle type. Diet had no effect (p>0.05) on the expression of stearoyl-CoA desaturase and lipoprotein lipase genes in LD and ST muscles in Dorper lambs. The T2 and T3 diets up regulated the expression of AMP-activated protein kinase alpha 2 gene in LD and ST muscles and up regulated the expression of sterol regulatory element-binding protein 1 in ST muscle in Dorper lambs.

    CONCLUSION: Dietary supplementation of Nigella sativa seeds and Rosmarinus officinalis leaves had beneficial effects on meat quality in Dorper lambs.

    Matched MeSH terms: AMP-Activated Protein Kinases
  8. Yap KH, Yee GS, Candasamy M, Tan SC, Md S, Abdul Majeed AB, et al.
    Biomolecules, 2020 09 24;10(10).
    PMID: 32987623 DOI: 10.3390/biom10101360
    Catalpol was tested for various disorders including diabetes mellitus. Numerous molecular mechanisms have emerged supporting its biological effects but with little information towards its insulin sensitizing effect. In this study, we have investigated its effect on skeletal muscle mitochondrial respiration and insulin signaling pathway. Type-2 diabetes (T2DM) was induced in male C57BL/6 by a high fat diet (60% Kcal) and streptozotocin (50 mg/kg, i.p.). Diabetic mice were orally administered with catalpol (100 and 200 mg/kg), metformin (200 mg/kg), and saline for four weeks. Fasting blood glucose (FBG), HbA1c, plasma insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), oxygen consumption rate, gene (IRS-1, Akt, PI3k, AMPK, GLUT4, and PGC-1α) and protein (AMPK, GLUT4, and PPAR-γ) expression in muscle were measured. Catalpol (200 mg/kg) significantly (p < 0.05) reduced the FBG, HbA1C, HOMA_IR index, and AUC of OGTT whereas, improved the ITT slope. Gene (IRS-1, Akt, PI3k, GLUT4, AMPK, and PGC-1α) and protein (AMPK, p-AMPK, PPAR-γ and GLUT4) expressions, as well as augmented state-3 respiration, oxygen consumption rate, and citrate synthase activity in muscle was observed in catalpol treated mice. The antidiabetic activity of catalpol is credited with a marked improvement in insulin sensitivity and mitochondrial respiration through the insulin signaling pathway and AMPK/SIRT1/PGC-1α/PPAR-γ activation in the skeletal muscle of T2DM mice.
    Matched MeSH terms: AMP-Activated Protein Kinases
  9. Abu Bakar MH, Shariff KA, Tan JS, Lee LK
    Eur J Pharmacol, 2020 Sep 15;883:173371.
    PMID: 32712089 DOI: 10.1016/j.ejphar.2020.173371
    Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism*
  10. Ramlan H, Damanhuri HA
    Exp Gerontol, 2020 01;129:110779.
    PMID: 31705967 DOI: 10.1016/j.exger.2019.110779
    BACKGROUND: Older people are likely to develop anorexia of aging. Rostral C1 (rC1) catecholaminergic neurons in rostral ventrolateral medulla (RVLM) are recently discovered its role in food intake control. It is well established that these neurons regulate cardiovascular function.

    OBJECTIVE: This study aims to determine the effect of age on the function of rostral C1 (rC1) neurons in mediating feeding response.

    METHOD: Male Sprague Dawley rats at 3-months (n = 22) and 24-months (n = 22) old were used and further divided into two subgroups; 1) treatment group with 2-deoxy-d-glucose (2DG) and 2) vehicle group. Feeding hormones such as cholecystokinin (CCK), ghrelin and leptin were analysed using enzyme-linked immunosorbent assay (ELISA). Rat brain was carefully dissected to obtain the brainstem RVLM region. Further analysis was carried out to determine the level of proteins and genes in RVLM that were associated with feeding pathway. Protein expression of tyrosine hydroxylase (TH), phosphorylated TH at Serine40 (pSer40TH), AMP-activated protein kinase (AMPK), phosphorylated AMPK (phospho AMPK) and neuropeptide Y Y5 receptor (NPY5R) were determined by western blot. Expression of TH, AMPK and NPY genes were determined by real-time PCR.

    RESULTS: This study showed that blood glucose level was elevated in young and old rats following 2DG administration. Plasma CCK-8 concentration was higher in the aged rats at basal and increased with 2DG administration in young rats, but the leptin and ghrelin showed no changes. Old rats showed higher TH and lower AMPK mRNA levels. Glucoprivation decreased AMPK mRNA level in young rats and decreased TH mRNA in old rats. Aged rC1 neurons showed higher NPY5R protein level. Following glucoprivation, rC1 neurons produced distinct molecular changes across age in which, in young rats, AMPK phosphorylation level was increased and in old rats, TH phosphorylation level was increased.

    CONCLUSION: These findings suggest that glucose-counterregulatory responses by rC1 neurons at least, contribute to the ability of young and old rats in coping glucoprivation. Age-induced molecular changes within rC1 neurons may attenuate the glucoprivic responses. This situation may explain the impairment of feeding response in the elderly.

    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  11. Lane SC, Camera DM, Lassiter DG, Areta JL, Bird SR, Yeo WK, et al.
    J Appl Physiol (1985), 2015 Sep 15;119(6):643-55.
    PMID: 26112242 DOI: 10.1152/japplphysiol.00857.2014
    We determined the effects of "periodized nutrition" on skeletal muscle and whole body responses to a bout of prolonged exercise the following morning. Seven cyclists completed two trials receiving isoenergetic diets differing in the timing of ingestion: they consumed either 8 g/kg body mass (BM) of carbohydrate (CHO) before undertaking an evening session of high-intensity training (HIT) and slept without eating (FASTED), or consumed 4 g/kg BM of CHO before HIT, then 4 g/kg BM of CHO before sleeping (FED). The next morning subjects completed 2 h of cycling (120SS) while overnight fasted. Muscle biopsies were taken on day 1 (D1) before and 2 h after HIT and on day 2 (D2) pre-, post-, and 4 h after 120SS. Muscle [glycogen] was higher in FED at all times post-HIT (P < 0.001). The cycling bouts increased PGC1α mRNA and PDK4 mRNA (P < 0.01) in both trials, with PDK4 mRNA being elevated to a greater extent in FASTED (P < 0.05). Resting phosphorylation of AMPK(Thr172), p38MAPK(Thr180/Tyr182), and p-ACC(Ser79) (D2) was greater in FASTED (P < 0.05). Fat oxidation during 120SS was higher in FASTED (P = 0.01), coinciding with increases in ACC(Ser79) and CPT1 as well as mRNA expression of CD36 and FABP3 (P < 0.05). Methylation on the gene promoter for COX4I1 and FABP3 increased 4 h after 120SS in both trials, whereas methylation of the PPARδ promoter increased only in FASTED. We provide evidence for shifts in DNA methylation that correspond with inverse changes in transcription for metabolically adaptive genes, although delaying postexercise feeding failed to augment markers of mitochondrial biogenesis.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  12. Sallehuddin, N. A., Azizah Abdul Hamid, Salleh, S. Z., Nazia Abdul Majid, Hani Hafeeza Halim, Nurul Shazini Ramli, et al.
    MyJurnal
    In the present work, aqueous ethanolic (60% ethanol) extracts from selected Malaysian herbs
    including Murraya koenigii L. Spreng, Lawsonia inermis L., Cosmos caudatus Kunth, Piper
    betle L., and P. sarmentosum Roxb. were evaluated for their ergogenic, anti-diabetic and
    antioxidant potentials. Results showed that the analysed herbs had ergogenic property and
    were able to activate 5'AMP-activated protein kinase (AMPK) in a concentration dependant
    manner. The highest AMPK activation was exhibited by M. koenigii extract which showed no
    significant (p > 0.05) difference with green tea (positive control). For anti-diabetic potential,
    the highest α-glucosidase inhibition was exhibited by M. koenigii extract with IC50 of 43.35
    ± 7.5 µg/mL, which was higher than acarbose (positive control). The determinations of free
    radical scavenging activity and total phenolics content (TPC) indicated that the analysed herbs
    had good antioxidant activity. However, C. caudatus extract showed superior antioxidant
    activity with IC50 against free radical and TPC of 21.12 ± 3.20 µg/mL and 221.61 ± 7.49 mg
    GAE/g, respectively. RP-HPLC analysis established the presence of flavonoids in the herbs
    wherein L. inermis contained the highest flavonoid (catechin, epicatechin, naringin and rutin)
    content (668.87 mg/kg of extract). Correlations between the analyses were conducted, and
    revealed incoherent trends. Overall, M. koenigii was noted to be the most potent herb for
    enhancement of AMPK activity and α-glucosidase inhibition but exhibited moderate antioxidant activity. These results revealed that the selected herbs could be potential sources of
    natural ergogenic and anti-diabetic/antioxidant agents due to their rich profile of phenolics.
    Further analysis in vivo should be carried out to further elucidate the mechanism of actions of
    these herbs as ergogenic aids and anti-diabetic/antioxidant agents.
    Matched MeSH terms: AMP-Activated Protein Kinases
  13. Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.
    J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
    PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015
    Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  14. Almabrouk TAM, White AD, Ugusman AB, Skiba DS, Katwan OJ, Alganga H, et al.
    Front Physiol, 2018;9:51.
    PMID: 29479319 DOI: 10.3389/fphys.2018.00051
    Background and aim:
    Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK.Methods:Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later.Key results:Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markersNos2andIl1band the M2 markerChil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice.Conclusions:High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD.
    Matched MeSH terms: AMP-Activated Protein Kinases
  15. Md Mokhtar AH, Malik IA, Abd Aziz NAA, Almabhouh FA, Durairajanayagam D, Singh HJ
    Andrologia, 2019 Apr;51(3):e13196.
    PMID: 30456785 DOI: 10.1111/and.13196
    This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin-induced adverse effects on rat spermatozoa. Sprague-Dawley rats, aged 14-16 weeks, were randomised into control, leptin-, leptin + dorsomorphin (AMPK inhibitor)-, and leptin+LY294002 (PI3K inhibitor)-treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg-1 body weight. Rats in the leptin and inhibitor-treated groups received concurrently either dorsomorphin (5 mg kg-1  day-1 ) or LY294002 (1.2 mg kg-1  day-1 ) i.p. for 14 days. Controls received 0.1 ml of normal saline. Upon completion, sperm count, sperm morphology, seminiferous tubular epithelial height (STEH), seminiferous tubular diameter (STD), 8-hydroxy-2-deoxyguanosine (8-OHdG) and phospho-Akt/total Akt ratio were estimated. Data were analysed using ANOVA. Sperm count, STEH and STD were significantly lower, while the percentage of spermatozoa with abnormal morphology and the level of 8-OHdG were significantly higher in rats treated with leptin and leptin + dorsomorphin when compared to those in controls and LY294002-treated rats. Testicular phospho-Akt/total Akt ratio was significantly higher in leptin and leptin + LY294002-treated rats. In conclusion, LY294002 prevents leptin-induced changes in rat sperm parameters, suggesting the potential role of the PI3K signalling pathway in the adverse effects of leptin on sperm parameters.
    Matched MeSH terms: AMP-Activated Protein Kinases/antagonists & inhibitors; AMP-Activated Protein Kinases/metabolism
  16. Lew LC, Hor YY, Jaafar MH, Lau ASY, Ong JS, Chuah LO, et al.
    Benef Microbes, 2019 Dec 09;10(8):883-892.
    PMID: 31965837 DOI: 10.3920/BM2019.0058
    This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.
    Matched MeSH terms: AMP-Activated Protein Kinases/genetics*
  17. Hor YY, Ooi CH, Khoo BY, Choi SB, Seeni A, Shamsuddin S, et al.
    J Med Food, 2019 Jan;22(1):1-13.
    PMID: 30592688 DOI: 10.1089/jmf.2018.4229
    Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated. The phosphorylation of AMPK by these three LAB strains was more evident in U2OS and C2C12 cells, compared to the other cell lines and control (P 
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
  18. Fayez A Almabhouh, Faizatul Isyraqiah Ahmad Muhammad, Hisham Ibrahim, Harbindarjeet Singh
    MyJurnal
    Leptin, a 16 kDa protein and a product of the ob/ob gene, has a tertiary structure similar to that
    of a cytokine. It is primarily secreted by white adipose tissue and its levels in the blood correlate
    positively with percentage body fat. Leptin was first identified in 1994 as a major factor that
    regulated food intake and energy balance. Leptin in the circulation exists either as a free
    monomeric hormone or bound to its soluble receptor. Its serum levels usually range from 0.5 to
    37.7 ng/ml in males and 2.0 to 45.2 ng/ml in females. The half-life of leptin is between 20 - 30
    minutes and it is eliminated mainly by the kidneys. However, research over the last 25 years
    has revealed numerous other physiological roles for leptin, including roles in inflammation,
    immune function, neuro-endocrine function, bone metabolism, blood pressure regulation and
    sexual maturation. Most of these roles have been identified from studies on leptin deficient
    rodents. Apart from energy balance and sexual maturation, where its role is direct and obvious,
    its actions on the rest of the other systems are permissive. Actions of leptin are both centrally
    and peripherally mediated involving receptors that are widely distributed in the body. Six leptin
    receptor isoforms, belonging to the class 1 cytokine receptor family, have been identified.
    These receptors are products of the OBR gene. The cellular actions of leptin are mediated
    through any one of five different signalling pathways that include the JAK-STAT, PI3K, MAPK,
    AMPK, and the mTOR signalling pathways.
    Matched MeSH terms: AMP-Activated Protein Kinases
  19. Chen SP, Lin SR, Chen TH, Ng HS, Yim HS, Leong MK, et al.
    Biomed Pharmacother, 2021 Dec;144:112333.
    PMID: 34678724 DOI: 10.1016/j.biopha.2021.112333
    Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism*
  20. Chok KC, Koh RY, Ng MG, Ng PY, Chye SM
    Molecules, 2021 Aug 20;26(16).
    PMID: 34443626 DOI: 10.3390/molecules26165038
    Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5'-adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.
    Matched MeSH terms: AMP-Activated Protein Kinases/metabolism
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