β-cell autophagy: A novel mechanism regulating β-cell function and mass- Lessons from β-cell-specific Atg7-deficient mice

Fujitani, Yoshio; Ebato, Chie; Uchida, Toyoyoshi; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.4161/isl.1.2.9057

Cited by 28 publications

(18 citation statements)

References 10 publications

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“…These findings suggest that autophagy is crucial for eliminating protein aggregates, harmful proteins, and organelles in β-cells in an insulin-resistant state, thereby avoiding cell death and the onset of diabetes. 17 In fact, abnormal ER stress response and mitochondrial dysfunction have been implicated as potential causes of insulin resistance. 18 Recently, autophagy was reported to participate in the downregulation of insulin receptors and ER stress-mediated insulin resistance as an adaptive process during ER stress.…”

Section: Autophagy and Type 2 Diabetesmentioning

confidence: 99%

The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

Yin

Wang

et al. 2012

Autophagy

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Shang-Ha Pan (2012) The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death, Autophagy, 8:2,[158][159][160][161][162][163][164] DOI: 10.4161 Keywords: autophagy, endoplasmic reticulum stress, pancreatic beta cell, free fatty acid, glucagon like peptide-1In pancreatic b-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the proteinfolding machinery for secretory proteins is localized. Perturbations to ER function of the b-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated b-cell death and focus on the role of autophagy in ameliorating ER stress. The development of drugs to take advantage of the potential protective effect of autophagy in ER stress, such as glucagon like peptide-1, will be a promising avenue of investigation.

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Section: Autophagy and Type 2 Diabetesmentioning

confidence: 99%

The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

Yin

Wang

et al. 2012

Autophagy

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“…Genetic ablation of Atg7 in pancreatic β cells resulted in degeneration of islets, impaired glucose tolerance, and reduced insulin secretion (85,86). Moreover, cardiomyocytes isolated from T2D db/db mice and HFD-induced obese mice exhibited reduced autophagic activity (87,88).…”

Section: Autophagy In Cardiovascular Diseasementioning

confidence: 99%

Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

286

211

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Autophagy in the vascular systemEndothelial cells. Autophagy can be regulated in vascular endothelial cells by compounds circulating in the bloodstream or localized within the subendothelial layer of atherosclerotic plaque. For example, in cultured HUVECs, vitamin D increases beclin 1, a key comCardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

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“…Autophagy occurs not only in order to recycle amino acids during starvation but also to clear away deteriorated proteins or organelles irrespective of nutritional stress. In fact, the deficiency of autophagy leads to the accumulation of disordered proteins that can ultimately cause a diverse range of diseases, including neurodegeneration and liver injury (12,29,30), and often to type 2 diabetes and malignant lymphoma (9,32).…”

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confidence: 99%

Dysfunction of Autophagy Participates in Vacuole Formation and Cell Death in Cells Replicating Hepatitis C Virus

Taguwa¹,

Kambara²,

Fujita

et al. 2011

J Virol

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Hepatitis C virus (HCV) is a major cause of chronic liver diseases. A high risk of chronicity is the major concern of HCV infection, since chronic HCV infection often leads to liver cirrhosis and hepatocellular carcinoma. Infection with the HCV genotype 1 in particular is considered a clinical risk factor for the development of hepatocellular carcinoma, although the molecular mechanisms of the pathogenesis are largely unknown. Autophagy is involved in the degradation of cellular organelles and the elimination of invasive microorganisms. In addition, disruption of autophagy often leads to several protein deposition diseases. Although recent reports suggest that HCV exploits the autophagy pathway for viral propagation, the biological significance of the autophagy to the life cycle of HCV is still uncertain. Here, we show that replication of HCV RNA induces autophagy to inhibit cell death. Cells harboring an HCV replicon RNA of genotype 1b strain Con1 but not of genotype 2a strain JFH1 exhibited an incomplete acidification of the autolysosome due to a lysosomal defect, leading to the enhanced secretion of immature cathepsin B. The suppression of autophagy in the Con1 HCV replicon cells induced severe cytoplasmic vacuolation and cell death. These results suggest that HCV harnesses autophagy to circumvent the harmful vacuole formation and to maintain a persistent infection. These findings reveal a unique survival strategy of HCV and provide new insights into the genotype-specific pathogenicity of HCV.Hepatitis C virus (HCV) is a major causative agent of bloodborne hepatitis and currently infects at least 180 million people worldwide (58). The majority of individuals infected with HCV develop chronic hepatitis, which eventually leads to liver cirrhosis and hepatocellular carcinoma (25,48). In addition, HCV infection is known to induce extrahepatic diseases such as type 2 diabetes and malignant lymphoma (20). It is believed that the frequency of development of these diseases varies among viral genotypes (14, 51). However, the precise mechanism of the genotype-dependent outcome of HCV-related diseases has not yet been elucidated. Despite HCV's status as a major public health problem, the current therapy with pegylated interferon and ribavirin is effective in only around 50% of patients with genotype 1, which is the most common genotype worldwide, and no effective vaccines for HCV are available (35, 52). Although recently approved protease inhibitors for HCV exhibited a potent antiviral efficacy in patients with genotype 1 (36, 43), the emergence of drug-resistant mutants is a growing problem (16). Therefore, it is important to clarify the life cycle and pathogenesis of HCV for the development of more potent remedies for chronic hepatitis C.HCV belongs to the genus Hepacivirus of the family Flaviviridae and possesses a single positive-stranded RNA genome with a nucleotide length of 9.6 kb, which encodes a single polyprotein consisting of approximately 3,000 amino acids (40). The precursor polyprotein is processed by host...

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β-cell autophagy: A novel mechanism regulating β-cell function and mass- Lessons from β-cell-specific Atg7-deficient mice

Cited by 28 publications

References 10 publications

The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death

Autophagy in cardiovascular biology

Dysfunction of Autophagy Participates in Vacuole Formation and Cell Death in Cells Replicating Hepatitis C Virus

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