Independent and combined effects of calorie restriction and AICAR on glucose uptake and insulin signaling in skeletal muscles from 24-month-old female and male rats DOI
Haiyan Wang,

Amy Zheng,

Dominic Thorley

et al.

Applied Physiology Nutrition and Metabolism, Journal Year: 2024, Volume and Issue: 49(5), P. 614 - 625

Published: Jan. 5, 2024

We assessed the effects of two levels calorie restriction (CR; eating either 15% or 35% less than ad libitum, AL, food intake for 8 weeks) by 24-month-old female and male rats on glucose uptake (GU) phosphorylation key signaling proteins (Akt; AMP-activated protein kinase, AMPK; Akt substrate 160 kDa, AS160) measured in isolated skeletal muscles that underwent four incubation conditions (without insulin AICAR, an AMPK activator; with AICAR alone; AICAR). Regardless sex: (1) neither CR group versus AL had greater GU insulin-stimulated muscles; (2) was increased rats; (3) prior treatment muscle resulted muscles, regardless diet; (4) caused elevated acetyl CoA carboxylase, indicator activation, all diet groups. There a sexually dimorphic effect AS160 phosphorylation, exceeding rats, but not rats. Our working hypothesis is lack CR-effect related to extended duration ex vivo period (290 min compared 40-50 previously reported be effective). The observed efficacy improve supports strategy targeting goal improving sensitivity older females males.

Language: Английский

Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes DOI Open Access

Teresa Vilariño‐García,

María Polonio-González,

Antonio Pérez‐Pérez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2338 - 2338

Published: Feb. 16, 2024

Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90–95% of cases are type 2 diabetes mellitus. This partly attributed the surge prevalence obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as primary cause morbidity and mortality, placing substantial burden on healthcare systems due potential for macrovascular microvascular complications. this context, leptin, an adipocyte-derived hormone, plays fundamental role. hormone essential regulating cellular metabolism energy balance, controlling inflammatory responses, maintaining CV system homeostasis. Thus, leptin resistance not only contributes weight gain but may also lead increased cardiac inflammation, greater fibrosis, hypertension, impairment metabolism. Understanding relationship between obese individuals with DM (T2DM) could improve management prevention complication. Therefore, narrative review, we will discuss evidence linking presence, severity, and/or prognosis obesity T2DM regarding disease, aiming shed light implications better preventive strategies.

Language: Английский

Citations

64
Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy DOI Creative Commons
Xi Lu,

Qingxing Xie,

Xiaohui Pan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 2, 2024

Language: Английский

Citations

54
Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age DOI Open Access
Giuseppe Lisco, Olga Disoteo, Anna De Tullio

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 16(1), P. 63 - 63

Published: Dec. 25, 2023

Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) associated with faster more relevant impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk falls, frailty, overall quality life, mortality. PubMed/Medline, Scopus, Web Science, Google Scholar were searched for research articles, scientific reports, observational studies, trials, narrative systematic reviews, meta-analyses review evidence pathophysiology di-abetes-induced sarcopenia, its relevance in terms glucose control diabetes-related outcomes, diagnostic therapeutic challenges. The comprehensively addresses key elements definition criteria pathophysiological correlation be-tween T2D, related a critical role antihyperglycemic treatment health, perspectives specific targeting myokine signaling pathways involved regulation metabolism trophism. Prompt diagnosis adequate management, including lifestyle inter-vention, diet programs, micronutrient supplementation, physical exercise, pharmaco-logical treatment, are needed prevent or delay T2D.

Language: Английский

Citations

34
Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action DOI Open Access
Zheng Zhao, Jun Yan, Lei Huang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116373 - 116373

Published: March 4, 2024

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative that occurs due to aging. Currently, effective drugs mitigate or treat AD remain unavailable. associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, defects cholesterol metabolism. Amp-activated protein kinase (AMPK) an important serine/threonine regulates the status of cells. AMPK widely present eukaryotic cells can sense regulate metabolism maintain supply demand balance, making it promising target for metabolism-based therapy. Therefore, this review aimed discuss molecular mechanism pathogenesis provide theoretical basis development new anti-AD drugs. To mechanisms phytochemicals treatment via pathway regulation, we searched PubMed, Google Scholar, Web Science, Embase databases using specific keywords related September 2023. Phytochemicals activate exert therapeutic effects AD. The these include inhibiting Aβ aggregation, preventing Tau hyperphosphorylation, inflammatory response glial activation, promoting autophagy, suppressing anti-oxidative stress. Additionally, AMPK-related pathways are involved mechanism, including AMPK/CaMKKβ/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin berberine, stigmasterol, arctigenin, rutaecarpine agonists effects. Several may have potential applications treatment. Overall, phytochemical-based overcome barriers diseases.

Language: Английский

Citations

16
AMPK-Mediated Multi-Organ Protective Effects of GLP-1 Receptor Agonists DOI Creative Commons

Xin Wang,

Linxi Wang

Published: Jan. 10, 2025

Review AMPK-Mediated Multi-Organ Protective Effects of GLP-1 Receptor Agonists Xin Wang 1 and Linxi 2,* Emergency Department, Fujian Medical University Union Hospital, Fuzhou 350001, China 2 Department Endocrinology Metabolism, Institute Endocrinology, * Correspondence: [email protected] Received: 11 October 2024; Revised: 23 Accepted: 20 December Published: 9 January 2025 Abstract: AMP-activated protein kinase (AMPK) is a key enzyme broadly involved in regulating cellular metabolism, often called an “energy sensor”. Activated AMPK promotes ATP production storage within cells, primarily by inhibiting ATP-consuming anabolic processes (such as protein, lipid, ribosomal synthesis) initiating ATP-producing catabolic pathways fatty acid oxidation glycolysis) to maintain energy homeostasis. regulates metabolic various peripheral tissues, including glucose lipid cholesterol metabolism pancreatic β-cells, the cardiovascular system, liver, kidneys, skeletal muscles, central nervous system. As antidiabetic drug, multi-organ protective effects Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly being recognized. This paper reviews mechanisms which GLP-1RA confers organ protection via signaling pathway.

Language: Английский

Citations

1
Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways DOI Creative Commons
Ahmed M. El‐Dessouki,

Mohamed E. Kaml,

Mohammed F. EL-Yamany

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Abstract This research investigated the hepatoprotective effects of esomeprazole (ESOM) and canagliflozin (CANA) against methotrexate-induced liver toxicity, focusing on AMPK modulation its regulation MAPK/JNK/ERK, JAK1/STAT3, PI3K/Akt pathways. Fifty male Wistar rats were divided into five groups: control, MTX, three pretreatment groups receiving ESOM (30 mg/kg), CANA or their combination. administered for 8 days before 1 day after a single MTX injection (20 mg/kg, intraperitoneally) 9 to induce hepatotoxicity. Liver injury, oxidative stress, inflammation, apoptosis assessed using biochemical, histopathological, immunohistochemical, qRT-PCR, western blot analyses. Data analyzed by one-way analysis variance (ANOVA) Tukey’s post hoc test, with significance at p < 0.05. Results presented as mean ± standard error (SE). Rats that received showed significant damage, marked elevated ALT, AST, MDA, MPO, iNOS, TNF-α, IL-6, IL-1β levels ( 0.01) decreased antioxidant enzymes (HO-1, Nrf2, GSH). Immunohistochemistry revealed increased NF-kB p65 caspase-9 expression 0.01), correlating histopathological changes. Pretreatment reduced enzyme levels, improved histology, restored balance, inhibited inflammatory pathways via p38MAPK/NF-kB JAK1/STAT3 0.01). Moreover, preserved activity prevented caspase-dependent Additionally, combination treatment synergistic effects, demonstrated improvements in all measured parameters. These findings suggested had potential therapeutic agents alleviating MTX-induced hepatotoxicity warranted further investigation future research.

Language: Английский

Citations

1
SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets DOI Open Access
Luning Yang,

Di Liu,

Shide Jiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 116917 - 116917

Published: June 21, 2024

Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various signaling pathways exert protective effect on many human diseases. SIRT1 functioned important role occurrence progression sarcopenia through regulating key related protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance autophagy muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), SIRT1/live B1 (LKB1)/AMPK pathways. However, specific mechanisms these processes have not fully illuminated. Currently, several SIRT1-mediated interventions preliminarily developed, such activator polyphenolic compounds, exercising calorie restriction. In this review, we summarized predominant involved therapeutic modalities targeting for prevention prognosis sarcopenia.

Language: Английский

Citations

8
6-Gingerol improves lipid metabolism disorders in skeletal muscle by regulating AdipoR1/AMPK signaling pathway DOI Open Access
Ze Peng, Yan Zeng, Xin Zeng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117462 - 117462

Published: Sept. 23, 2024

Language: Английский

Citations

8
Molecular mechanisms linking type 2 diabetes mellitus and late-onset Alzheimer's disease: A systematic review and qualitative meta-analysis DOI Creative Commons
Erwin Lemche, Richard Killick,

Jackie Mitchell

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 196, P. 106485 - 106485

Published: April 21, 2024

Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim this systematic review is to provide a comprehensive mechanisms, have hitherto been discussed in separate perspectives, and assemble evaluate candidate loci epigenetic modifications contributing polygenic linkages between T2DM LOAD. For the on pathophysiological both human animal studies up December 2023 are included. qualitative meta-analysis genomic bases, association were examined; for data from models accepted. Papers describing identified databases, further literature gathered cited work. epigenomic studies, mining was conducted by formalised search codes using Boolean operators engines, augmented GeneRif citations Entrez Gene, other sources (WikiGenes, etc.). 923 publications evaluated, 138 gene extracted testing linkages. 3 57 evaluated descriptions modifications. Overall results highlight insulin signalling, inflammation inflammasome pathways, proteolysis, gluconeogenesis glycolysis, glycosylation, lipoprotein metabolism oxidation, cell cycle regulation or survival, autophagic-lysosomal energy. Documented findings suggest interplay brain resistance, neuroinflammation, insult compensatory peripheral dysregulation LOAD linkage. allow more streamlined longitudinal T2DM-LOAD

Language: Английский

Citations

7
PPARβ/δ attenuates hepatic fibrosis by reducing SMAD3 phosphorylation and p300 levels via AMPK in hepatic stellate cells DOI Open Access

Meijian Zhang,

Emma Barroso,

Lucía Peña

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117303 - 117303

Published: Aug. 18, 2024

The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject debate. Here, we examined the effects PPARβ/δ agonist on pathogenesis liver and activation stellate cells (HSCs), main effector fibrosis, response to pro-fibrotic stimulus transforming growth factor-β (TGF-β). GW501516 completely prevented glucose intolerance peripheral insulin resistance, blocked accumulation collagen liver, attenuated expression inflammatory fibrogenic genes mice fed choline-deficient high-fat diet (CD-HFD). antifibrogenic effect observed livers CD-HFD-fed could occur through an action HSCs since primary isolated from Ppard

Language: Английский

Citations

7