Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway

Lei, Yueyue; Gong, Leilei; Tan, Fanggen; Liu, Yixiao; Li, Shuangshuang; Shen, Houwang; Zhu, Min; Cai, Weiwei; Xu, Fei; Hou, Bao; Zhou, Yuetao; Han, Hongxiu; Qiu, Ling; Sun, Hai-Jian

doi:10.1016/j.ejphar.2019.02.029

Cited by 36 publications

(21 citation statements)

References 64 publications

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“…AMPK is a key regulator of energy metabolism and is abundantly expressed in metabolically related tissues. What is more, the activation of AMPK promotes oxidation of fatty acid beta 42,43 and phosphorylation of AMPK could activate a large number of downstream target proteins, inhibit the synthesis of fat and cholesterol, and promote fatty acid oxidation and glucose transport 44 . It has been demonstrated that activation of AMPK directly promotes GLUT4 expression in the skeletal muscle 45 .…”

Section: Discussionmentioning

confidence: 99%

Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway

Wang

et al. 2020

Nutr. Diabetes

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Objectives: The study aimed to examine the anti-diabetic effects of Gynura divaricata (GD) and the underlying mechanism. Methods: Information about the chemical compositions of GD was obtained from extensive literature reports. Potential target genes were predicted using PharmMapper and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). To validate the results from bioinformatics analyses, an aqueous extract of GD was administered to type 2 diabetic rats established by feeding a high-fat and high-sugar diet followed by STZ injection. Key proteins of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway were investigated by immunoblotting. Results: The blood glucose of the rats in the GD treatment group was significantly reduced compared with the model group without treatment. GD also showed activities in reducing the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CREA). The levels of urine sugar (U-GLU) and urine creatinine (U-CREA) were also lowered after treatment with GD. Bioinformatics analysis showed that some pathways including metabolic pathways, insulin resistance, insulin signaling pathway, PPAR signaling pathway, bile secretion, purine metabolism, etc. may be regulated by GD. Furthermore, GD significantly increased the protein expression levels of PKM1/2, p-AKT, PI3K p85, and GLUT4 in the rat liver. In addition, the expression levels of key proteins in the fatty acid metabolism signaling pathway including AMPK, p-AMPK, PPARα, and CPT1α were significantly upregulated. The antiapoptotic protein BCL-2/BAX expression ratio in rats was significantly upregulated after GD intervention. These results were consistent with the bioinformatics analysis results. Conclusions: Our study suggests that GD can exert hypoglycemic effects in vivo by regulating the genes at the key nodes of the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway

Wang

et al. 2020

Nutr. Diabetes

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“…The glucose production of AML12 cells was detected as described previously. 15 Briefly, after treatment cells were washed and incubated for 2 hours in glucose-, L-glutamine-, phenol red-, sodium pyruvate-and sodium bicarbonate-free DMEM supplemented with or without gluconeogenic substrates (200 μmol/L glycerol only or 10 mmol/L sodium lactate and 2 mmol/L sodium pyruvate). Glucose in the medium was measured using a colorimetric glucose assay kit (Cat: K606-100, BioVison) and normalized with total cellular protein.…”

Section: Glucose Production Assaymentioning

confidence: 99%

P53/PANK1/miR‐107 signalling pathway spans the gap between metabolic reprogramming and insulin resistance induced by high‐fat diet

Yang

Zhang

Wang

et al. 2020

J Cellular Molecular Medi

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High‐fat diet (HFD) leads to obesity, type II diabetes mellitus (T2DM) and increases the coincidence of cardiovascular diseases and cancer. Insulin resistance (IR) is considered as the ‘common soil’ of those diseases. Furthermore, people on HFD showed restrained glycolysis and enhanced fatty acid oxidation, which is the so‐called metabolic reprogramming. However, the relationship between metabolic reprogramming and IR induced by HFD is still unclear. Here, we demonstrate that PANK1 and miR‐107 were up‐regulated in the liver tissue of mice on HFD for 16 weeks and involved in metabolic reprogramming induced by palmitate acid (PA) incubation. Importantly, miR‐107 within an intron of PANK1 gene facilitated IR by targeting caveolin‐1 in AML12 cells upon PA incubation. Moreover, we identify that HFD enhanced P53 expression, and activation of P53 with nutlin‐3a induced PANK1 and miR‐107 expression simultaneously in transcriptional level, leading to metabolic reprogramming and IR, respectively. Consistently, inhibition of P53 with pifithrin‐α hydrobromide ameliorated PA‐induced metabolic reprogramming and IR. Thus, our results revealing a new mechanism by which P53 regulate metabolism. In addition, the results distinguished the different roles of PANK1 and its intron miR‐107 in metabolic regulation, which will provide more accurate intervention targets for the treatment of metabolic diseases.

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“…The freshly isolated Liver tissues were immersed in 4% aqueous buffered paraformaldehyde at the room temperature for overnight fixation and then dehydrated, embedded in paraffin and sliced into 4 μm sections. The paraffin-embedded tissue sections were routinely stained with HE staining to conduct histologic analysis [25] . [26,27] .…”

Section: He Stainingmentioning

confidence: 99%

Tertiary Butylhydroquinone Ameliorates Insulin Resistance and Liver Steatosis in Type 2 Diabetes Mellitus

Zhu

Liu

et al. 2020

Preprint

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Aims: This study aimed to evaluate the effects and mechanisms of tertiary butylhydroquinone (TBHQ) on insulin resistance (IR) and diabetic liver steatosis. Methods: Male ApoE-/- mice were received streptozocin (STZ) injection and a high-sugar-high-fat diet to form type 2 diabetes mellitus (T2DM). Then, the mice were given TBHQ for six weeks. Body weight, fasting blood-glucose (FBG), postprandial blood glucose (PBG), insulin and oral glucose tolerance test (OGTT) were detected on all the mice. Hematoxylin-eosin staining and western-blot were performed to detect the morphological structure and the target proteins expression in liver tissues. In vitro, HepG2 cells were induced by HClO and insulin to develop IR. Western-blot was used to evaluate the related proteins expression. Hoechst staining was conducted to measure cell apoptosis. Results: Mice that received STZ injection and a high-sugar-high-fat diet developed T2DM. TBHQ reduced blood glucose level, improved glucose tolerance, alleviated liver steatosis in diabetic mice. Moreover, TBHQ significantly increased AMPKα2, GLUT4 and GSK3β expression, up-regulated PI3K and AKT phosphorylation level in diabetic mice liver. Notably, TBHQ down-regulated HClO and insulin-induced cell IR and inhibited cell apoptosis via AMPKα2/PI3K/AKT pathway. Conclusion: TBHQ alleviated IR and liver steatosis in T2DM mice and the mechanism may relate to AMPKα2/PI3K/AKT pathway.

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Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway

Cited by 36 publications

References 64 publications

Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway

Gynura divaricata exerts hypoglycemic effects by regulating the PI3K/AKT signaling pathway and fatty acid metabolism signaling pathway

P53/PANK1/miR‐107 signalling pathway spans the gap between metabolic reprogramming and insulin resistance induced by high‐fat diet

Tertiary Butylhydroquinone Ameliorates Insulin Resistance and Liver Steatosis in Type 2 Diabetes Mellitus

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