Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function

Xu, Haixia; Du, Xiao; Xu, Jia; Zhang, Yu; Tian, Yan; Li, Geng; Wang, Xiuxuan; Ma, Ming; Du, Wenya; Liu, Yu; Dai, Lunzhi; Huang, Wendong; Tong, Nanwei; Wei, Yuquan; Fu, Xianghui

doi:10.1371/journal.pbio.3000603

Cited by 111 publications

(105 citation statements)

References 76 publications

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“…Intriguingly, it has recently been shown that phosphorylated STAT3 is present in exosomes from 5-fluorouracil (5-FU) resistant colorectal cancer cells, which contributes to acquired 5-FU resistance [ 149 ]. Given the importance and efficiency of exosomes in intercellular and interorgan communication [ 150 , 151 ], these findings not only add another complexity to STAT3 regulation, but also pave a new way to inhibit the oncogenic function of STAT3, as well as to delivery STAT3 inhibitors via exosomes.…”

Section: Targeting Stat3 For Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 is broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors. Therefore, targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers. In this review, we outline the importance of STAT3 signaling pathway in tumorigenesis and its immune regulation, and highlight the current status for the development of STAT3-targeting therapeutic approaches. We also summarize and discuss recent advances in STAT3-based combination immunotherapy in detail. These endeavors provide new insights into the translational application of STAT3 in cancer and may contribute to the promotion of more effective treatments toward malignancies.

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Section: Targeting Stat3 For Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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“…Diabetic complications are closely correlated with insulin resistance and may reflect the severity of pregestational diabetes and poor glycemic control. 55 Similarly, previous studies have found a higher risk of genital anomalies and cardiovascular diseases in offspring of mothers with diabetic complications. 21 33 Maternal poor glycemic control in pregnancy may exert potential implications in offspring for behavioral and emotional problems.…”

Section: Discussionmentioning

confidence: 82%

Maternal diabetes and the risk of feeding and eating disorders in offspring: a national population-based cohort study

Wang

et al. 2020

BMJ Open Diab Res Care

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IntroductionPrevious studies have suggested that maternal diabetes may have programming effect on fetal brain development. However, little is known about the association between maternal diabetes and neurodevelopmental disorders in offspring that mainly manifest in infancy or early childhood. We aimed to examine the association between maternal diabetes before or during pregnancy and feeding and eating disorders (FED) in offspring.Research design and methodsThis population-based cohort study included 1 193 891 singletons born in Denmark during 1996–2015. These children were followed from birth until the onset of FED, the sixth birthday, death, emigration, or 31 December 2016, whichever came first. Relative risk of FED was estimated by HRs using Cox proportional hazards model.ResultsA total of 40 867 (3.4%) children were born to mothers with diabetes (20 887 with pregestational diabetes and 19 980 with gestational diabetes). The incidence rates of FED were 6.8, 4.6 and 2.9 per 10 000 person-years among children of mothers with pregestational diabetes, gestational diabetes and no diabetes, respectively. Offspring of mothers with diabetes had a 64% increased risk of FED (HR 1.64; 95% CI 1.36 to 1.99; p<0.001). The HR for maternal pregestational diabetes and gestational diabetes was 2.01 (95% CI 1.59 to 2.56; p<0.001) and 1.28 (95% CI 0.95 to 1.72; p=0.097), respectively. The increased risk was more pronounced among offspring of mothers with diabetic complications (HR 2.97; 95% CI 1.54 to 5.72; p=0.001).ConclusionsMaternal diabetes was associated with an increased risk of FED in offspring in infancy and early childhood. Our findings can inform clinical decisions for better management of maternal diabetes, in particular before pregnancy, which can reduce early neurodevelopmental problems in the offspring.

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“…However, the secretion of miRNAs from the pancreas was not investigated until very recently. A study reported that β cell‐secreted miR‐26s influenced peripheral insulin sensitivity (Xu et al., 2020). Herein, we found that pancreatic β cells respond to high levels of FFAs by secreting exosomal miR‐29s to target the hepatic insulin signalling pathway and promote insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR‐29 family

Zhang

et al. 2021

J of Extracellular Vesicle

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Secreted microRNAs (miRNAs) are novel endocrine factors that play essential pathological and physiological roles. Here, we report that pancreatic β cell-released exosomal miR-29 family members (miR-29s) regulate hepatic insulin sensitivity and control glucose homeostasis. Cultured pancreatic islets were shown to secrete miR-29s in response to high levels of free fatty acids (FFAs) in vitro. In vivo, high levels of FFAs, promoted by either high-fat diet (HFD) feeding (physiopathological) or fasting (physiological), increased the secretion of miR-29s into plasma. Intravenous administration of exosomal miR-29s attenuated insulin sensitivity. The overexpression of miR-29s in the β cells of transgenic (TG) mice promoted the secretion of miR-29s and inhibited the insulin-mediated suppression of glucose output in the liver. We used selective overexpression of traceable heterogenous mutant miR-29s in β cells to confirm that islet-derived exosomal miR-29s target insulin signalling in the liver and blunt hepatic insulin sensitivity. Moreover, in vivo disruption of miR-29s expression in β cells reversed HFD-induced insulin resistance. In vitro experiments demonstrated that isolated exosomes enriched in miR-29s inhibited insulin signalling in the liver and increased hepatic glucose production. These results unveil a novel β cellderived secretory signal-exosomal miR-29s-and provide insight into the roles of miR-29s in manipulating glucose homeostasis.

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Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function

Cited by 111 publications

References 76 publications

Targeting STAT3 in Cancer Immunotherapy

Targeting STAT3 in Cancer Immunotherapy

Maternal diabetes and the risk of feeding and eating disorders in offspring: a national population-based cohort study

Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR‐29 family

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