Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function

He, Xiaoyu; Lai, Qiaohong; Chen, Cai; Li, Na; Sun, Fei; Huang, Wenting; Zhang, Shu; Yu, Qilin; Yang, Ping; Xiong, Fei; Chen, Zhishui; Gong, Quan; Ren, Boxu; Weng, Jianping; Eizirik, Décio L.; Zhou, Zhiguang; Wang, Cong Yi

doi:10.1007/s00125-017-4523-9

Cited by 58 publications

(53 citation statements)

References 45 publications

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“…Following fixation, the tissue was processed by dehydration with a gradient concentration of ethanol, cleared in xylene, embedded in paraffin, and sliced at 4 µm thickness. HE staining was performed according to the manufacturer's protocols (Solarbio, Beijing, China) (He et al, 2018).…”

Section: Hematoxylin and Eosin (He) Stainingmentioning

confidence: 99%

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

Wang

Lei

Yan

et al. 2020

Front. Cell. Infect. Microbiol.

159

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Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.

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Section: Hematoxylin and Eosin (He) Stainingmentioning

confidence: 99%

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

Wang

Lei

Yan

et al. 2020

Front. Cell. Infect. Microbiol.

159

View full text Add to dashboard Cite

show abstract

“…β-actin was used for normalization, and the relative expression levels for each target gene were calculated using the 2 −ΔΔCt approach as previously reported. 24 The primers used to amplify each target gene were as…”

Section: Quantitative Rt-pcr Analysismentioning

confidence: 99%

Blockade of JAK2 protects mice against hypoxia‐induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation

Zhang

Wang

et al. 2020

Cell Proliferation

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Objectives Hypoxia is an important risk factor for pulmonary arterial remodelling in pulmonary arterial hypertension (PAH), and the Janus kinase 2 (JAK2) is believed to be involved in this process. In the present report, we aimed to investigate the role of JAK2 in vascular smooth muscle cells during the course of PAH. Methods Smooth muscle cell (SMC)‐specific Jak2 deficient mice and their littermate controls were subjected to normobaric normoxic or hypoxic (10% O2) challenges for 28 days to monitor the development of PAH, respectively. To further elucidate the potential mechanisms whereby JAK2 influences pulmonary vascular remodelling, a selective JAK2 inhibitor was applied to pre‐treat human pulmonary arterial smooth muscle cells (HPASMCs) for 1 hour followed by 24‐hour hypoxic exposure. Results Mice with hypoxia‐induced PAH were characterized by the altered JAK2/STAT3 activity in pulmonary artery smooth muscle cells. Therefore, induction of Jak2 deficiency in SMCs protected mice from hypoxia‐induced increase of right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodelling. Particularly, loss of Jak2 significantly attenuated chronic hypoxia‐induced PASMC proliferation in the lungs. Similarly, blockade of JAK2 by its inhibitor, TG‐101348, suppressed hypoxia‐induced human PASMC proliferation. Upon hypoxia‐induced activation, JAK2 phosphorylated signal transducer and activator of transcription 3 (STAT3), which then bound to the CCNA2 promoter to transcribe cyclin A2 expression, thereby promoting PASMC proliferation. Conclusions Our studies support that JAK2 could be a culprit contributing to the pulmonary vascular remodelling, and therefore, it could be a viable target for prevention and treatment of PAH in clinical settings.

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“…Histology and immunofluorescence staining were performed as previously described (23). Briefly, the same half of pancreatic tissues from vehicle-or AS-treated mice were fixed with 4% paraformaldehyde, embedded in paraffin, and sectioned at a thickness of 5 mm.…”

Section: Histology and Immunofluorescence Of Pancreatic Tissuesmentioning

confidence: 99%

Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL‐4—producing T cells and regulatory T cells

Shi

Liu

et al. 2019

FASEB j.

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune‐mediated destruction of insulin‐producing β cells. Recent studies showed that in addition to malaria, artemisinin and its derivative, artesunate (AS), could alleviate several autoimmune diseases. However, whether AS has a role in the prevention or treatment of T1D is still unknown. Therefore, in this study we administrated AS or DMSO in the drinking water of nonobese diabetic (NOD) mice, a mouse model of T1D. We found that AS administration significantly prevented the incidence of T1D. The frequency of IL‐4—producing CD4+ single‐positive T cells and CD8+ T cells was significantly elevated, and IFN‐γ—producing T cells were reduced in the spleen and pancreatic lymph nodes. In the pancreas, the skewing to IL‐4—producing T cells was also observed. In addition, more regulatory T cells were found in the pancreas. mRNA levels of proinflammatory cytokines, including TNF‐α and IL‐6, were decreased. In addition, AS administration promoted the functional maturity of β cells in vitro. Our findings demonstrate that AS administration can prevent T1D in NOD mice mainly by reducing autoimmune T cells and increasing protective T cells. Our data constitute the first functional study of AS in T1D, which may provide a new rationale for future translational studies.—Li, Z., Shi, X., Liu, J., Shao, F., Huang, G., Zhou, Z., Zheng, P. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL‐4—producing T cells and regulatory T cells. FASEB J. 33, 8241–8248 (2019). http://www.fasebj.org

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Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function

Cited by 58 publications

References 45 publications

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets

Blockade of JAK2 protects mice against hypoxia‐induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation

Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL‐4—producing T cells and regulatory T cells

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