Rheb1 promotes glucose-stimulated insulin secretion in human and mouse β-cells by upregulating GLUT expression

Yang, Yan; Cai, Zhongxiang; Pan, Zhenhong; Liu, Fen; Li, Dandan; Ji, Yujiao; Zhong, Jiaxin; Luo, Hairong; Hu, Shanbiao; Song, Lei; Yu, Shaojie; Li, Ting; Li, Jiequn; Ma, Xianhua; Zhang, Weiping; Zhou, Zhiguang; Liu, Feng; Zhang, Jingjing

doi:10.1016/j.metabol.2021.154863

Cited by 11 publications

(6 citation statements)

References 56 publications

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“…However, these antioxidant enzymes are under-expressed in β-cells, resulting in the increased sensitivity of β-cells to the threats posed by excessive ROS production. Other factors with protective roles against oxidative stress, Rheb1 and Fam3a for instance, are also found to downregulate in β-cells under diabetic conditions ( Yang et al., 2020 , 2021 ). In addition, due to the inherent vulnerability of mitochondrial DNA (mtDNA) against elevated ROS levels, oxidative stress is believed to induce lesions to mtDNA so that mitochondrial dysfunction in diabetic conditions is developed ( Chow et al., 2017 ).…”

Section: Mechanisms Of β-Cell Dysfunction In T2dmentioning

confidence: 98%

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

Sun

Zhang

et al. 2022

Journal of Molecular Cell Biology

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Pancreatic β-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes (T2D). Recent clinical and experimental studies have suggested that the functional capacity of β-cells, particularly in the first phase of insulin secretion, is a primary contributor to the progression of T2D and its associated complications. Pancreatic β-cells undergo dynamic compensation and decompensation processes during the development of T2D, in which metabolic stresses such as endoplasmic reticulum (ER) stress, oxidative stress, and inflammatory signals are key regulators of β-cell dynamics. Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D, especially in the early stages. Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague, accumulating evidence has implicated the improvement of β-cell functional capacity. In this review, we summarize recent advances in the understanding of the dynamic adaptations of β-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions on β-cell dysfunction in T2D. This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D, and more importantly, it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.

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Section: Mechanisms Of β-Cell Dysfunction In T2dmentioning

confidence: 98%

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

Sun

Zhang

et al. 2022

Journal of Molecular Cell Biology

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“…Pancreatic β cell lose is a main characteristic of both type I and type II diabetes [21,22]. Stem cells are a renewable source of pluripotent cells, which can be utilized to insulin-producing β cells repair and regeneration during diabetes treatment [23,24].…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed microRNAs during the differentiation of muscle-derived stem cells into insulin-producing cells, a promoting role of microRNA-708-5p/STK4 axis

et al. 2022

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Objective Stem cell therapy is a promising approach for diabetes via promoting the differentiation of insulin-producing cells (IPCs). This study aimed to screen the differentially expressed miRNAs (DEmiRNAs) during the differentiation of muscle-derived stem cells (MDSCs) into IPCs, and uncover the underlying function and mechanism of a specific DEmiRNA, miR-708-5p. Methods MDSCs were successfully isolated from the leg muscle of rats, and were induced for IPCs differentiation through a five-stage protocol. miRNA microarray assay was performed for screening DEmiRNAs during differentiation. The features of MDSCs-derived IPCs were identified by qRT-PCR, flow cytometry, and immunofluorescence staining. The targeting of STK4 by miR-708-5p was examined by luciferase assay. The protein expression of STK4, YAP1, and p-YAP1 was determined by Western blot and immunofluorescence staining. Results MDSCs were successfully isolated and differentiated into IPCs. A total of 12 common DEmiRNAs were obtained during five-stage differentiation. Among them, miR-708-5p that highly expressed in MDSCs-derived IPCs was selected. Overexpression of miR-708-5p upregulated some key transcription factors (Pdx1, Ngn3, Nkx2.2, Nkx6.1, Gata4, Gata6, Pax4, and Pax6) involving in IPCs differentiation, and increased insulin positive cells. In addition, STK4 was identified as the target gene of miR-708-5p. miR-708-5p overexpression downregulated the expression of STK4 and the downstream phosphorylated YAP1. Conclusions There were 12 DEmiRNAs involved in the differentiation of MDSCs into IPCs. miR-708-5p promoted MDSCs differentiation into IPCs probably by targeting STK4-mediated Hippo-YAP1 signaling pathway.

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“…This intricate gambit exacerbates insulin resistance ( 34 ). Within this intricate theater, the PHD/HIF system unfurls its influence upon the process of glucose-stimulated insulin secretion within beta cells ( 50 ). While HIF-α famously wields its influence, augmenting glucose-stimulated insulin secretion by driving the expression of GLUT1 and GLUT3 ( 51 ), its influence dances on a precipice, also eliciting insulin resistance by disrupting AKT phosphorylation ( 52 ).…”

Section: Iron and Its Biological Effectsmentioning

confidence: 99%

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

Ouyang,

Zhou,

Wang

2023

Front. Endocrinol.

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Iron, as the most abundant metallic element within the human organism, is an indispensable ion for sustaining life and assumes a pivotal role in governing glucose and lipid metabolism, along with orchestrating inflammatory responses. The presence of diabetes mellitus (DM) can induce aberrant iron accumulation within the corporeal system. Consequentially, iron overload precipitates a sequence of important adversities, subsequently setting in motion a domino effect wherein ferroptosis emerges as the utmost pernicious outcome. Ferroptosis, an emerging variant of non-apoptotic regulated cell death, operates independently of caspases and GSDMD. It distinguishes itself from alternative forms of controlled cell death through distinctive morphological and biochemical attributes. Its principal hallmark resides in the pathological accrual of intracellular iron and the concomitant generation of iron-driven lipid peroxides. Diabetic retinopathy (DR), established as the predominant cause of adult blindness, wields profound influence over the well-being and psychosocial strain experienced by afflicted individuals. Presently, an abundance of research endeavors has ascertained the pervasive engagement of iron and ferroptosis in the microangiopathy inherent to DR. Evidently, judicious management of iron overload and ferroptosis in the early stages of DR bears the potential to considerably decelerate disease progression. Within this discourse, we undertake a comprehensive exploration of the regulatory mechanisms governing iron homeostasis and ferroptosis. Furthermore, we expound upon the subsequent detriments induced by their dysregulation. Concurrently, we elucidate the intricate interplay linking iron overload, ferroptosis, and DR. Delving deeper, we engage in a comprehensive deliberation regarding strategies to modulate their influence, thereby effecting prospective interventions in the trajectory of DR’s advancement or employing them as therapeutic modalities.

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Rheb1 promotes glucose-stimulated insulin secretion in human and mouse β-cells by upregulating GLUT expression

Cited by 11 publications

References 56 publications

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

Differentially expressed microRNAs during the differentiation of muscle-derived stem cells into insulin-producing cells, a promoting role of microRNA-708-5p/STK4 axis

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

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