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FX5 as a non-steroidal GR antagonist improved glucose homeostasis in type 2 diabetic mice via GR/HNF4 α/miR-122-5p pathway.
FX5 as a non-steroidal GR antagonist improved glucose homeostasis in type 2 diabetic mice via GR/HNF4α/miR-122-5p pathway. Aging (Albany NY). 2020 Dec 09;12: Authors: Xu X, Chen Y, Zhu D, Zhao T, Xu R, Wang J, Hu L, Shen X Abstract Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by glucose metabolic disorders, and gluconeogenesis inhibiting is a promisingly therapeutic strategy for T2DM. Glucocorticoid receptor (GR) is tightly implicated in the regulation of gluconeogenesis, although the underlying mechanism remains obscure. Here, we discovered that small molecule, 5-chlo...
Source: Aging - December 9, 2020 Category: Biomedical Science Authors: Xu X, Chen Y, Zhu D, Zhao T, Xu R, Wang J, Hu L, Shen X Tags: Aging (Albany NY) Source Type: research

miR-27-3p inhibition restore fibroblasts viability in diabetic wound by targeting NOVA1.
Abstract Diabetic wounds increase morbidity and decrease quality of life in patients with type 2 diabetes. Serum miR-27-3p levels are reportedly elevated in type 2 diabetic patients. In the present study, we explored the role of miR-27-3p during wound healing. We found that miR-27-3p is overexpressed in cutaneous fibroblasts of diabetic patients and mice. miR-27-3p knockdown enhanced the proliferation and migration of fibroblasts, while suppressing the incidence of fibroblast apoptosis. Overexpressing miR-27-3p in fibroblasts had the opposite effects. We also identified neuro-oncological ventral antigen 1 (NOVA1) ...
Source: Aging - June 25, 2020 Category: Biomedical Science Authors: Zhang P, Song X, Dong Q, Zhou L, Wang L Tags: Aging (Albany NY) Source Type: research

Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose.
Abstract Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix-loop-helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mes...
Source: Bioscience Reports - November 12, 2018 Category: Biomedical Science Authors: Chen Y, Wang YJ, Zhao Y, Wang JC Tags: Biosci Rep Source Type: research

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease.
Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (class II-III) and db/db mice compared to the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol-regulatory element binding protein-1 (SREBP-1) was clearly upregulated, w...
Source: Clinical Science - October 22, 2018 Category: Biomedical Science Authors: Yang, W., Luo, Y., Yang, S., Zeng, M., Zhang, S., Liu, J., Han, Y., Liu, Y., Zhu, X., Wu, H., Liu, F., Sun, L., Xiao, L. Tags: PublishAheadOfPrint Source Type: research

siRNA-mediated inhibition of SREBP cleavage-activating protein reduces dyslipidemia in spontaneously dysmetabolic rhesus monkeys
SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo. Type 2 diabetics with dyslipidemia are at high risk for cardiovascular diseases.
Source: Metabolism - Clinical and Experimental - March 5, 2017 Category: Biomedical Science Authors: Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G. McLaren, Stephen F. Previs, Shirly Pinto Source Type: research

siRNA-mediated inhibition of SCAP reduces dyslipidemia in spontaneously dysmetabolic rhesus monkeys
SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo. Type 2 diabetics with dyslipidemia are at high risk for cardiovascular diseases.
Source: Metabolism - Clinical and Experimental - March 4, 2017 Category: Biomedical Science Authors: Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G. McLaren, Stephen F. Previs, Shirly Pinto Source Type: research

Ampelopsin Improves Insulin Resistance by Activating PPARγ and Subsequently Up-Regulating FGF21-AMPK Signaling Pathway
by Yong Zhou, Ying Wu, Yu Qin, Lei Liu, Jing Wan, Lingyun Zou, Qianyong Zhang, Jundong Zhu, Mantian Mi Ampelopsin (APL), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. Here, we explored the anti-diabetic activity of APL and elucidate the underlying mechanism of this action. In palmitate-induced insulin resistance of L6 myotubes, APL treatment markedly up- regulated phosphorylated insulin receptor substrate-1 and protein kinase B, along with a corresponding increase of glucose uptake capacity. APL treatment also increased expressions of fibroblast growth factor (FGF21) and...
Source: PLoS One - July 7, 2016 Category: Biomedical Science Authors: Yong Zhou Source Type: research

Human umbilical cord matrix-derived stem cells exert trophic effects on {beta}-cell survival in diabetic rats and isolated islets RESEARCH ARTICLE
ABSTRACT Human umbilical cord matrix-derived stem cells (uMSCs), owing to their cellular and procurement advantages compared with mesenchymal stem cells derived from other tissue sources, are in clinical trials to treat type 1 (T1D) and type 2 diabetes (T2D). However, the therapeutic basis remains to be fully understood. The immunomodulatory property of uMSCs could explain the use in treating T1D; however, the mere immune modulation might not be sufficient to support the use in T2D. We thus tested whether uMSCs could exert direct trophic effects on β-cells. Infusion of uMSCs into chemically induced diabetic rats preve...
Source: DMM Disease Models and Mechanisms - December 4, 2015 Category: Biomedical Science Authors: Zhou, Y., Hu, Q., Chen, F., Zhang, J., Guo, J., Wang, H., Gu, J., Ma, L., Ho, G. Tags: RESEARCH ARTICLE Source Type: research

Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4-induced insulin secretion in INS-1 cells
Conclusion: Our study suggests that the stimulation of β-cell insulin secretion by Ex-4 is mediated, at least in part, by CASK via a novel signaling mechanism.
Source: Metabolism - Clinical and Experimental - October 21, 2013 Category: Biomedical Science Authors: Zheng-Qiu Zhu, Dong Wang, Dan Xiang, Yue-Xing Yuan, Yao Wang Tags: Basic Science Source Type: research