Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of a novel insulin receptor-binding protein from Momordica charantia by transcriptomic, proteomic, and docking analyses

ABSTRACT: Momordica charantia (MC) is a common vegetable in tropical areas and has been used for a long time as an alternative therapy for diabetes. Although several constituents of MC have displayed the hypoglycemic effects, the hypoglycemic targets of these constituents remain to be clarified. In this study, we analyzed and elucidated the therapeutic targets contributing to the hypoglycemic effect of aqueous extract of MC seeds (MCSE) by transcriptomic analysis. The protein ingredients aimed at the hypoglycemic target were further identified by proteomic, docking, and receptor-binding assays. Our data showed that MCSE, which was rich in small-molecular weight proteins, displayed hypoglycemic effects in normal and diabetic mice by glucose tolerance assay. MCSE significantly and primarily regulated the insulin signaling pathway in muscles and adipose tissues, suggesting that MCSE might target to insulin receptor (IR), stimulate the IR-downstream pathway, and subsequently display the hypoglycemic activity. We further identified that inhibitor against trypsin (TI) of MC directly docked into IR and activated the kinase activity of IR. In conclusion, our findings suggested that MCSE regulated glucose metabolism mainly via insulin signaling pathway. Moreover, we newly identified that TI was a novel IR-binding protein of MC that triggers the insulin signaling pathway via binding to IR.

ORGANISM(S): Mus musculus

PROVIDER: GSE39689 | GEO | 2015/07/01

SECONDARY ACCESSION(S): PRJNA171580

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of a novel insulin receptor-binding protein from Momordica charantia by transcriptomic, proteomic, and docking analyses

Project description:Momordica charantia (MC) is a common vegetable in tropical areas and has been used for a long time as an alternative therapy for diabetes. Although several constituents of MC have displayed the hypoglycemic effects, the hypoglycemic targets of these constituents remain to be clarified. In this study, we analyzed and elucidated the therapeutic targets contributing to the hypoglycemic effect of aqueous extract of MC seeds (MCSE) by transcriptomic analysis. The protein ingredients aimed at the hypoglycemic target were further identified by proteomic, docking, and receptor-binding assays. Our data showed that MCSE, which was rich in small-molecular weight proteins, displayed hypoglycemic effects in normal and diabetic mice by glucose tolerance assay. MCSE significantly and primarily regulated the insulin signaling pathway in muscles and adipose tissues, suggesting that MCSE might target to insulin receptor (IR), stimulate the IR-downstream pathway, and subsequently display the hypoglycemic activity. We further identified that inhibitor against trypsin (TI) of MC directly docked into IR and activated the kinase activity of IR. In conclusion, our findings suggested that MCSE regulated glucose metabolism mainly via insulin signaling pathway. Moreover, we newly identified that TI was a novel IR-binding protein of MC that triggers the insulin signaling pathway via binding to IR. Mice were fasted for 4 h and MCSE or PBS was then orally given 15 min before intraperitoneal administration of glucose solution (1 g/kg body weight). Blood samples were collected from tails at 15 min before and at 15, 30, 60, 90, 120, 150, 180, and 240 min after glucose challenge. Blood glucose was measured by glucose oxidase method using a glucometer (ACCU-CHEK Advantage, Roche Diagnostics, Basel, Switzerland). Mice were sacrificed 4 h after glucose challenge. Muscles, adipose tissues, and livers were collected for microarray analysis.

2015-07-01 | E-GEOD-39689 | biostudies-arrayexpress

Using DNA microarray to screen intracellular signal pathways of hypoglycemic activity by electroacupuncture of Zusanli (ST36) acupoints in streptozotocin-induced rats with diabetes

Project description:The aim of this study is to screen the possible effective intracellular signaling pathways of EA on bilateral Zusanli acupoint (ST36) by DNA microarray in rats with diabetes. Streptozotocin (STZ) rats with diabetes were randomly assigned to the experimental (EA) group or the control (non-EA) group. The exploratory methods for analysis in this study were the following points: (i) detecting plasma glucose levels (ii) pathway analysis by DNA microarray in rats' gastrocnemius muscle. The pathway analysis of DNA microarray showed that the insulin signaling pathway, PPAR signaling pathway, MAPK signaling pathway or Wnt signal pathway might be related to the hypoglycemic effect of STZ rats with diabetes induced by EA. Using DNA microarray would be helpful in screening the possible targets of signaling pathways. The hypoglycemic effect of EA was close relative to insulin and relative intracellular signal pathways. Further research will be required to determine the details of the intracellular signaling pathways of the hypoglycemic effect induced by EA.

2017-03-01 | GSE55573 | GEO

A novel insulin receptor-binding protein enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway

2016-06-25 | GSE48274 | GEO

A novel insulin receptor-binding protein enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway

Project description:In this study, a novel IR-binding protein (IRBP) from Momordica charantia, named as mcIRBP, was identified by analyzing the physical and functional interactions between mcIRBP and IR. The hypoglycemic effect and mechanism of mcIRBP were further evaluated in normal and streptozotocin-induced diabetic mice. Normal and diabetic mice were treated without or with mcIRBP and RNAs from muscle tissues were extracted for microarray analysis. Number of replicate was three.

2016-06-25 | E-GEOD-48274 | biostudies-arrayexpress

Muscle Specific Insulin Receptor Overexpression Protects Mice from Diet-Induced Glucose Intolerance but Leads to Post-Receptor Insulin Resistance

Project description:Skeletal muscle insulin resistance is a prominent early feature in the pathogenesis of type 2 diabetes (T2D). In attempt to overcome this defect, we generated mice overexpressing insulin receptors (IR) specifically in skeletal muscle (IRMOE). On normal chow, IRMOE mice have similar body weight as controls, but an increase in lean mass and glycolytic muscle fibers and reduced fat mass. IRMOE mice also show higher basal phosphorylation of IR, IRS-1 and Akt in muscle and improved glucose tolerance compared to controls. When challenged with high fat diet (HFD), IRMOE mice are protected from diet-induced obesity. This is associated with reduced inflammation in fat and liver, improved glucose tolerance and improved systemic insulin sensitivity. Surprisingly, however, in both chow and HFD-fed mice, insulin stimulated Akt phosphorylation is significantly reduced in muscle of IRMOE mice, indicating post-receptor insulin resistance. RNA sequencing reveals downregulation of several post-receptor signaling proteins that contribute to this resistance. Thus, enhancing early insulin signaling in muscle by overexpression of the insulin receptor protects mice from diet-induced obesity and its effects on glucose metabolism. However, chronic overstimulation of this pathway leads to post-receptor desensitization, indicating the critical balance between normal signaling and hyperstimulation of the insulin signaling pathway.

2020-09-01 | GSE149662 | GEO

Salivary Transcriptomic Biomarkers for Insulin Resistance

Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between insulin resistance high risk subjects and insulin resistance low risk subjects Participants enrolled in this study were recruited in the overnight fasted state, then the collection and processing of glucose (fasting, 30, 60 and 120 minutes) and insulin from blood samples, hemoglobin A1c (HbA1c) , assessment of medical history, socio-demographic characteristics, lifestyle factors, blood pressure and anthropometric and body composition measurements were conducted. During baseline visit, participants were asked to refrain from eating, drinking and oral hygiene procedures for at least 1-hour prior to saliva collection.5 ml of unstimulated whole saliva samples were consistently collected, stabilized and preserved, the sample supernatants were reserved at -80°C prior to assay. Based on the homeostasis model assessment of insulin resistance (HOMA-IR), using the formula [HOMA-IR= (fasting glucose*fasting insulin)/405], participants were divided into 2 groups: IR high risk group (HOMA-IR value ?2.5) and IR low risk group (HOMA-IR value <2.5). Total RNA was extracted from saliva and subjected to gene expression microarray analysis using Affymetrix human genome 2.0 plus array

2015-04-10 | E-GEOD-67738 | biostudies-arrayexpress

Combined use of astragalus polysaccharide and berberine attenuates insulin resistance in IR-HepG2 cells via regulation of the gluconeogenesis signaling pathway

Project description:Insulin resistance (IR) is likely to induce metabolic syndrome and type 2 diabetes mellitus (T2DM). Gluconeogenesis (GNG) is a complex metabolic process that may result in glucose generation from certain non-carbohydrate substrates. Chinese herbal medicine astragalus polysaccharides and berberine have been documented to ameliorate IR, and combined use of astragalus polysaccharide (AP) and berberine (BBR) are reported to synergistically produce an even better effect. However, what change may occur in the GNG signaling pathway of IR-HepG2 cells in this synergistic effect and whether AP-BBR attenuates IR by regulating the GNG signaling pathway remain unclear. For the first time, we discovered in this study that the optimal time of IR-HepG2 cell model formation was 48 hours after insulin intervention. AP-BBR attenuated IR in HepG2 cells and the optimal concentration was 10mg. AP-BBR reduced the intracellular H2O2 content with no significant effect on apoptosis of IR-HepG2 cells. In addition, a rapid change was observed in intracellular calcium current of the IR-HepG2 cell model, and AP-BBR intervention attenuated this change markedly. The gene sequencing results showed that the GNG signaling pathway was one of the signaling pathways of AP-BBR to attenuate IR in IR-Hepg2 cells. The expression of p-FoxO1Ser256 and PEPCK protein was increased and the expression of GLUT2 protein was decreased significantly in the IR-HepG2 cell model, and both of these effects could be reversed by AP-BBR intervention. AP-BBR attenuated IR in IR-HepG2 cells, probably by regulating the GNG signaling Pathway.

2019-11-14 | GSE139929 | GEO

The epigenetic signature of systemic insulin resistance in obese women [SC]

Project description:Impaired ability of insulin to stimulate cellular glucose uptake and regulate metabolism, that is insulin resistance (IR), links adiposity to metabolic disorders such as type 2 diabetes (T2D), dyslipidemia and cardiovascular disease (Langenberg, 2012). Both genetic and epigenetic factors are implicated in development of systemic IR (Vaag, 2001). IR is characterized by elevated levels of fasting insulin in the general circulation. The aim of this study is to explore whether white adipose tissue (WAT) epigenetic dysregulation is associated with systemic IR by global CpG methylation and gene expression profiling in subcutaneous and visceral adipose tissue. A secondary aim is to determine whether the DNA methylation signature in peripheral blood mononuclear cells reflect WAT methylation, and can be used as marker for systemic IR.

2016-08-01 | GSE76398 | GEO

The epigenetic signature of systemic insulin resistance in obese women [OM]

2016-08-01 | GSE76394 | GEO

The epigenetic signature of systemic insulin resistance in obese women [BL]

2016-08-01 | GSE76285 | GEO