SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice

Qin, Kunhua; Zhang, Ning; Zhang, Zhao; Nipper, Michael; Zhu, Zhenxin; Leighton, Jake; Xu, Kexin; Musi, Nicolas; Wang, Pei

doi:10.1007/s00125-017-4542-6

Cited by 42 publications

(45 citation statements)

References 43 publications

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“…Conversely, Sirt6 overexpression protects against palmitate-induced β-cell dysfunction and apoptosis (Song et al, 2016 ; Xiong et al, 2016 ). Recently, a new study found that Sirt6 is critical for pancreatic β-cell function and survival in mice (Qin et al, 2018 ). Sirt6 deficiency does not affect endocrine morphology, β-cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice (Qin et al, 2018 ).…”

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

“…Recently, a new study found that Sirt6 is critical for pancreatic β-cell function and survival in mice (Qin et al, 2018 ). Sirt6 deficiency does not affect endocrine morphology, β-cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice (Qin et al, 2018 ). β-cell specific deletion of Sirt6 reproduced the defect in insulin secretion.…”

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

“…β-cell specific deletion of Sirt6 reproduced the defect in insulin secretion. Loss of Sirt6 increases acetylation of histone H3K9Ac, H3K56Ac, and activates RNA polymerase II at the promoter region of thioredoxin-interacting protein (TXNIP) (Qin et al, 2018 ). TXNIP expression is negatively associated with glucose-stimulated insulin secretion in β-cells and that overexpression of TXNIP inhibits insulin secretion (Rani et al, 2010 ; Yoshihara et al, 2010 ; Luo et al, 2014 ).…”

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

“…Sirt6-deficiency in β-cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac, and TXNIP levels. Finally, β-cell specific Sirt6-deficient mice showed increased sensitivity to streptozotocin induced β-cell apoptosis (Qin et al, 2018 ). Together, this report indicates that Sirt6 has a key role in pancreatic function.…”

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

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The Role of Sirt6 in Obesity and Diabetes

et al. 2018

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Sirt6 is one of the sirtuin family members, a kind of NAD+-dependent histone deacetylase and ADP-ribose transferase enzyme. It has an important role in physiological and pathological processes, regulating aging, cancer, obesity, insulin resistance, inflammation, and energy metabolism. Recent studies have suggested that reduced Sirt6 action is related to obesity and diabetes. Aging and overnutrition, two major risk factors for obesity and diabetes, lead to decreased Sirt6 level and function, which results in abnormal glucose and lipid metabolism. Whole-body ablation of Sirt6 in mice results in severe hypoglycemia. Sirt6 deficiency leads to liver steatosis and promotes diet-induced obesity and insulin resistance. Sirt6 has a protective effect on obesity and diabetes. This review surveys evidence for an emerging role of Sirt6 as a regulator of metabolism in mammals and summarizes its major functions in obesity and diabetes.

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Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

Section: Sirt6 and Glucose Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Sirt6 in Obesity and Diabetes

et al. 2018

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“…β-cells of pancreas showed decreased sensitivity when Sirt6 is inhibited. Sirt6 deficiency increases H3K9Ac, H3K56Ac levels and active RNA polymerase II at the promoter region of Txnip, causing expression of Txnip that promotes β-cell apoptosis [47].…”

Section: Sirt6mentioning

confidence: 99%

Sirtuins and diabetes: optimizing the sweetness in the blood

Kanwal

Dsouza

2019

transl med commun

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Diabetes Mellitus (DM) is a chronic disease characterized by elevated levels of glucose in the blood. With time it becomes uncontrollable and invites other complex metabolic diseases. The propensity of the people for this disease is age independent. However, sirtuins, which get activate typically during calorie restriction plays a pivotal role in optimizing effect of blood glucose levels in diabetic patients. Among different sirtuin homologs, some of the sirtuins are known for regulating pathophysiology of diabetic condition. Still the role of other sirtuins in understanding the function and regulatory mechanism in DM is still emerging. In this review, we focused on recent studies which help us to understand about the role of sirtuins and how they regulate the pathophysiology in diabetic condition.

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Emerging roles of SIRT6 in human diseases and its modulators

Liu

Chen

Liu

et al. 2020

Medicinal Research Reviews

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The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6‐mediated diseases.

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SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice

Abstract: Sequence data have been deposited in the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) with the accession code GSE104161.

Cited by 42 publications

References 43 publications

The Role of Sirt6 in Obesity and Diabetes

The Role of Sirt6 in Obesity and Diabetes

Sirtuins and diabetes: optimizing the sweetness in the blood

Emerging roles of SIRT6 in human diseases and its modulators

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