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Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA.

ABSTRACT: High-density lipoproteins provide protection against the damaging effects of glucolipotoxicity in beta cells, a factor which sustains insulin secretion and staves off onset of type 2 diabetes mellitus. This study examines epigenetic changes in small non-coding microRNA sequences induced by high density lipoproteins in a human hybrid beta cell model, and tests the impact of delivery of a single sequence in protecting against glucolipotoxicity. Human PANC-1.1B4 cells were used to establish Bmax and Kd for [³H]cholesterol efflux to high density lipoprotein, and minimum concentrations required to protect cell viability and reduce apoptosis to 30mM glucose and 0.25 mM palmitic acid. Microchip array identified the microRNA signature associated with high density lipoprotein treatment, and one sequence, hsa-miR-21-5p, modulated via delivery of a mimic and inhibitor. The results confirm that low concentrations of high-density lipoprotein can protect against glucolipotoxicity, and report the global microRNA profile associated with this lipoprotein; delivery of miR-21-5p mimic altered gene targets, similar to high density lipoprotein, but could not provide sufficient protection against glucolipotoxicity. We conclude that the complex profile of microRNA changes due to HDL treatment may be difficult to replicate using a single microRNA, findings which may inform current drug strategies focused on this approach.

SUBMITTER: Tarlton JMR

PROVIDER: S-EPMC8000094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice.

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Circulating microRNA-375 as biomarker of pancreatic beta cell death and protection of beta cell mass by cytoprotective compounds.

Project description:Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug.PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death. Beta cell mass and apoptotic death were measured in pancreatic tissue sections. Circulating miR-375 was measured in blood plasma by RT-qPCR. The release of miR-375 was also measured in vitro by MIN-6 beta cells.Administration of STZ resulted in measurable circulating levels of miR-375, a decrease in beta cell mass and increase in frequency of apoptotic beta cells. In vitro, there was a good correlation between miR-375 release and the extent of beta cell death. Treatment of mice with PPAG or exendin-4 significantly attenuated STZ-induced loss of beta cell mass and beta cell apoptosis, and normalized the blood level of miR-375.These findings show the potential use of serological miR-375 measurements to evaluate the beta cytoprotective effect of (potential) antidiabetic drugs in vivo.

| S-EPMC5645134 | biostudies-literature

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Project description:The pancreatic beta cell function failure is the core event of type 2 diabetes mellitus. High levels of free fatty acid and glucose are two main factor that induced pancreatic beta cell function failure. Long term exposure to palmitate can induced pancreatic beta cell apoptoss and impaired insulin secretion in vivo and in vitro, called lipotoxicity. The lipotoxicity often coupled with high glucose, their combination form called glucolipotoxcity. We carried out temporal transcriptome and proteome studies investigating the evolution of molecular events in Ins1 cells stimulated by palmitate for different times. And through compared the transcriptome and proteome between lipotoxicity and glucolipotoxicity explain the mechanism of glucolipotoxicity more harmfull to beta cell.

2019-04-27 | GSE98272 | GEO

Expression data from TGF-beta treated Panc-1 pancreatic adenocarcinoma cell line

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| S-ECPF-GEOD-23952 | biostudies-other

Synthetic High-density Lipoprotein Nanodiscs for Personalized Immunotherapy Against Gliomas.

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