Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Brown adipocyte-derived exosomes in type 2 diabetes mellitus impair endothelial function via elevated intracellular calcium load

ABSTRACT: Atherosclerosis is a leading cause of macrovascular complications in type 2 diabetes mellitus (T2DM). Lipid metabolism disorders in T2DM alter exosomal cargos, affecting vascular endothelial cells and impairing vascular endothelium-dependent relaxation. This study investigates the link between T2DM and atherosclerosis, focuing on adipose tissue-derived exosomes (AT-Exosomes) as key pathogenic factors in T2DM.

ORGANISM(S): Mus musculus

PROVIDER: GSE287534 | GEO | 2026/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Glucagon regulates Hepatic Kisspeptin1 to Impair Insulin Secretion in Diabetes Mellitus

Project description:Glucagon and insulin are counter-regulatory pancreatic hormones that precisely control blood glucose homeostasis1. Type 2 diabetes mellitus (T2DM) is characterized by inappropriately elevated blood glucagon2-5 levels as well as insufficient glucose stimulated insulin secretion (GSIS) by pancreatic ß-cells6. Early in the pathogenesis of T2DM, hyperglucagonemia is observable antecedent to ß-cell dysfunction7-9; and in mice, liver-specific activation of glucagon receptor-dependent signaling results in impaired GSIS10. However, the mechanistic relationship between hyperglucagonemia, hepatic glucagon action, and ß-cell dysfunction remains poorly understood. Here we show that glucagon action stimulates hepatic production of the neuropeptide kisspeptin1, which acts in an endocrine manner on ß-cells to suppress GSIS. In vivo glucagon administration acutely stimulates hepatic kisspeptin1 production, and kisspeptin1 is increased in livers from humans with T2DM and from mouse models of diabetes mellitus. Synthetic kisspeptin1 potently suppresses GSIS in vivo and in vitro from normal isolated islets, which express the kisspeptin1 receptor Kiss1R. Administration of a Kiss1R antagonist in diabetic Leprdb/db mice potently augments GSIS and reduces glycemia. Our observations indicate in the pathogenesis of T2DM an endocrine mechanism sequentially linking hyperglucagonemia via hepatic kisspeptin1 production to impaired insulin secretion. In addition, our findings suggest Kiss1R antagonism as a therapeutic avenue to improve ß-cell function in T2DM. Total RNA from L-Δprkar1a KO mice compared to control D-glucose mice

2014-04-01 | E-GEOD-48815 | biostudies-arrayexpress

Glucagon regulates Hepatic Kisspeptin1 to Impair Insulin Secretion in Diabetes Mellitus

2014-04-01 | GSE48815 | GEO

Proteomics and metabolomics analysis of rat upper carotid artery following Mongolian acupuncture therapy for T2DM atherosclerosis

Project description:Diabetes mellitus (DM) is a chronic, noncommunicable disease, mainly due to insufficient insulin secretion or insulin sensitivity. Atherosclerosis is one of the major macrovascular complications of DM, and it is the main cause of death from clinical observation. Mongolian acupuncture therapy has the function of dredging meridians and regulating blood circulation, which has been proved to have unique efficacy and notable advantages in the treatment of DM and its common chronic complications. However, the effects and molecular mechanism of Mongolian acupuncture therapy in T2DM atherosclerosis remain unclear. The aim of this study is to explore the effect and molecular mechanism of streptozotocin and vitamin D3-induced T2DM atherosclerosis in rats, with or without Mongolian acupuncture therapy. The results of serum biochemical and histopathology analysis suggest that acupuncture therapy can improve cellular inflammatory factors, kidney function, serum lipid function and upper carotid artery tissue lesions in rat with T2DM atherosclerosis, which is an effective treatment method. In addition, we applied proteomics and metabolomics to comprehensively demonstrate that Mongolian acupuncture therapy in T2DM atherosclerosis mainly through regulation of lipid metabolism and amino acid metabolism. In general, our findings provide beneficial data support for future clinical studies of Mongolian acupuncture therapy in T2DM atherosclerosis.

| PXD052040 |

Vascular endothelial growth factor B regulates insulin secretion in β cells of type 2 diabetes mellitus mice via PLCγ and IP3R-evoked Ca2+/CaMK2 signal pathway

Project description:Vascular endothelial growth factor B (VEGFB) plays a crucial role in glucolipid metabolism and is highly associated with type 2 diabetes mellitus (T2DM). The role of VEGFB in the insulin secretion of β cells remains unverified. Thus, this study aims to discuss the effect of VEGFB on regulating insulin secretion in T2DM development, and its underlying mechanism. A high-fat diet and streptozocin were used for inducing T2DM in mice model, and VEGFB gene in islet cells of T2DM mice was knocked out by CRISPR Cas9 and overexpressed by Adeno-Associated Virus (AAV) injection. The effect of VEGFB and its underlying mechanism was assessed by light microscope, electron microscope, fluorescence confocal microscope, enzyme-linked immunosorbent assay, mass spectrometer, and western blot. The decrement of insulin secretion in islet β cell of T2DM mice are aggravated and blood glucose remains at a high level after VEGFB deletion. However, glucose tolerance and insulin sensitivity of T2DM mice were improved after the AAV-VEGFB186 injection. VEGFB knockout or overexpression can inhibit or activate PLCγ/IP3R in a VEGFR1-dependent manner. Then, the change of PLCγ/IP3R caused by VEGFB/VEGFR1 will alter the expression of key factors on the Ca2+/CaMK2 signal pathway such as PPP3CA. Moreover, VEGFB can cause altered insulin secretion by changing the calcium concentration in β cells of T2DM mice. These findings indicated that VEGFB activated the Ca2+/CaMK2 pathway via VEGFR1-PLCγ and IP3R pathway to regulate insulin secretion, which provides new insight into the regulatory mechanism of abnormal insulin secretion in T2DM.

2023-10-24 | PXD043843 | Pride

NPC-derived exosome-mediated effects on macrophages

Project description:Transcriptomic analysis delineated the interactions between NPC cells and macrophages through exosome cargos. The findings revealed that NPC cells modulated macrophage polarization via exosomes, thereby promoting tumor progression

2024-11-23 | GSE282685 | GEO

Impaired Fetal Lung Development can be Rescued by Administration of Extracellular Vesicles Derived from Amniotic Fluid Stem Cells

Project description:Primary epithelial cells isolated from fetal lungs of rat fetuses with or without lung hypoplasia induced by the administration of nitrofen to pregnant rats. Control group included epithelial cells from normal fetal lungs. Treatment with amniotic fluid stem cell derived extracellular vesicles or with mesenchymal stromal cell derived exosomes, RNA-seq of both cargos included.

2021-03-23 | E-MTAB-8921 | biostudies-arrayexpress

Brown adipocyte-derived exosomes in type 2 diabetes mellitus impair endothelial function via elevated intracellular calcium load

Project description:Brown adipocyte-derived exosomes in type 2 diabetes mellitus impair endothelial function via elevated intracellular calcium load

| PRJNA1213687 | ENA

A mitochondrial proteome profile of type 2 diabetes mellitus in skeletal muscles

Project description:The goal of the project is to understand the mitochondrial proteome profiles related to T2DM. We performed comprehensive proteome profiling of mitochondria isolated from skeletal muscles in nine T2DM patients and nine control subjects with normal glucose tolerance (NGT).

2018-10-02 | PXD004312 | Pride

Molecular Mechanism of type 2 diabetes mellitus-mediated heart failure with preserved ejection fraction

Project description:Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with several comorbidities, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-induced cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS (mavacamten, which is a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment (herein after denotes as MYK-461), was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression, suggesting its promise as a therapeutic treatment for HFpEF.

2024-08-01 | GSE235934 | GEO

A mitochondrial proteome profile of type 2 diabetes mellitus in skeletal muscles

2019-03-13 | MSV000083560 | MassIVE