Expression of farnesyl pyrophosphate synthase is increased in diabetic cardiomyopathy

Zhang, Jiefang; Wang, Min; Qiu, Fuyu; Jin, Chongyin; Fu, Guosheng

doi:10.1002/cbin.11573

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…FPPS expression was elevated in cardiomyocytes and aorta cells from diabetic mice with diabetic cardiomyopathy 118 and atherosclerosis, 119 respectively. FPPS inhibition by alendronate improved fasting plasma glucose, HbA1c, and insulin resistance, 13 lowered the high glucose-stimulated proliferation of VSMCs, 7 and reduced glucose uptake and formation of advanced glycation end products by retinal cells.…”

Section: Small Gtpases and Enzymes Of The Mevalonate Pathway In Pathological States Of Diabetes And Its Complicationsmentioning

confidence: 99%

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

2021

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A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein–protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Hyperglycemia-induced upregulation of small GTPases suggests that inhibition of these pathways deserves to be considered as a potential therapeutic approach in treating T2D. This Perspective presents how inhibition of various points in the mevalonate pathway might affect protein prenylation and functioning of diabetes-affected tissues and contribute to chronic inflammation involved in diabetes mellitus (T2D) development. We also demonstrate the currently available molecular tools to decipher the mechanisms linking the mevalonate pathway’s enzymes and GTPases with diabetes.

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Section: Small Gtpases and Enzymes Of The Mevalonate Pathway In Pathological States Of Diabetes And Its Complicationsmentioning

confidence: 99%

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

2021

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Inhibition of farnesyl pyrophosphate synthase alleviates cardiomyopathy in diabetic rat

Liu

Tang

et al. 2022

Cell Cycle

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Farnesyl Diphosphate Synthase (FDPS) Regulates Granulosa Cells Proliferation of Polycystic Ovary Syndrome (PCOS) by Modulating the Rac1/MAPK/ERK signaling

Guo,

Cao,

et al. 2023

Preprint

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Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. Due to a poor understanding of the mechanisms involved, there is a limited selection of etiology-specific treatments for infertility in individuals with PCOS. Here, proteomic analysis indicated that the differential protein ovarian Farnesyl Diphosphate Synthase (FDPS) was closely related to the pathogenesis of PCOS. Notably, FDPS protein expression was significantly decreased in ovarian granulosa cells from PCOS patients resulted in disrupted ovarian functions and dysplasia of ovarian granulosa cells. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 activity and regulated MAPK/ERK signaling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the Adeno-Associated Virus (AAV)-FDPS reverse the DHEA-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.

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Expression of farnesyl pyrophosphate synthase is increased in diabetic cardiomyopathy

Cited by 3 publications

References 39 publications

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

Inhibition of farnesyl pyrophosphate synthase alleviates cardiomyopathy in diabetic rat

Farnesyl Diphosphate Synthase (FDPS) Regulates Granulosa Cells Proliferation of Polycystic Ovary Syndrome (PCOS) by Modulating the Rac1/MAPK/ERK signaling

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