CELLULAR SIGNALLING
·
2025
·
IF 3.7
Jie Liu,Mei-qi He,Gao-peng Guan,Xin-xing Wan,Ping Jin
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms. Despite a significant increase in ISG15 levels following viral infection, the specific role of ISG15 in the impairment of insulin-producing β-cells is unclear. To address this issue at the clinical level, we conducted this experimental work, and found elevated levels of ISG15 in the peripheral blood of T1D patients, suggesting a potential link between ISG15 and T1D. In the T1D animal model, we discovered that both ISG15 levels and cellular apoptosis were increased in pancreatic islet tissue. To investigate at the cellular level, we cultured MIN6 cells in the presence of supernatants derived from iBMDM cells transfected with poly(I:C) (PIC), a viral mimic. This exposure led to an upregulation of ISG15 expression in MIN6 cells, which was accompanied by the suppression of their functional capabilities and viability. Intriguingly, the direct transfection of MIN6 cells with PIC increased the expression of ISG15. We further found that elevated levels of ISG15 had a direct inhibitory effect on insulin secretion and it also contributed to β-cell apoptosis in a TNF-α-dependent manner. In conclusion, our study revealed a potential underlying mechanism through which ISG15 increases the apoptosis of β-cells, providing valuable insights that could facilitate the development of T1D treatment strategies.
研究领域:
免疫学
·
内分泌学
·
糖尿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yu Zhang,Bingjie Yang,Wei Sun,Xun Sun,Jing Zhao,Quanhong Li
A novel natural water-soluble acidic polysaccharide (PWESP-3) was isolated from squash with a molecular mass of 140.519 kDa, which was composed of arabinose (Ara, 35.30 mol%), galactose (Gal, 61.20 mol%), glucose (Glc, 1.80 mol%), and Mannuronic acid (ManA, 1.70 mol%) and contained Araf-(1→, →3)-Araf-(1→, →5)-Araf-(1→, Glcp-(1→, Galp-(1→, →3,5)-Araf-(1→, →2)-Glcp-(1→, →2)-Manp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →3)-Galp-(1→, →6)-Galp-(1→, →3,4)-Galp-(1→, →4,6)-Galp-(1→ residues in the backbone. Moreover, the structure of PWESP-3 was identified by NMR spectra. The branch chain was connected to the main chain by the O-3 and O-4 atom of Gal. In addition, the effect of PWESP-3 on STZ-induced type I diabetes mellitus model in MIN6 cells was investigated. The results showed that PWESP-3 can increase the viability and insulin secretion of MIN6 cells and reduce the oxidative stress caused by ROS and NO. Meanwhile, PWESP-3 can also reduce the content of ATP, Ca 2+ , mitochondrial membrane potential and Caspase-3 activity in MIN6 cells. Furthermore, treatment with PWESP-3 can prevent single or double stranded DNA breaking to form DNA fragments and improve DNA damage in MIN6 cells, thereby avoiding apoptosis. Therefore, the above data highlight that PWESP-3 can improve the function of insulin secretion in STZ-induced MIN6 cells in vitro and can be used as an alternative food supplement to diabetes drugs.
研究领域:
生物化学
·
药理学
·
细胞生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Xilin Jiang,Jian Tang,Zhiqiang Gao,Caixia Chen,Wenjun Li,Lu Peng,Hongwei Li,Hongying Zhao,Yun Zhao
Moringa oleifera Lam. ( M. oleifera ) has been used as a remedy for diabetes clinically. To discover the underlying mechanism, we investigated its hypoglycemic compounds and shed light on its regulatory targets and pathways using network pharmacology. A total of 13 active compounds of stem were shot, and they may relieve diabetes through 122 core intersecting targets, mainly regulating the biological processes of inflammatory response and apoptosis. Molecular docking showed binding advantages of the active compounds with proteins in apoptosis process. In experiments conducted on MIN6 cells, an islet β-cell line, the extract of M. oleifera stem was validated to protect cells from apoptosis through reducing cellular ROS and endoplasmic reticulum stress. And consistently with its protective effect on islet β-cells, M. oleifera stem alleviated hyperglycemia in Type 2 diabetes mellitus (T2DM) mice. These results offer novel evidence for the development of functional foods to treat T2DM with M. oleifera stem.
研究领域:
药理学
·
糖尿病
·
网络药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Yang Siwen,Qu Yunhe,Chen Jiyu,Chen Si,Sun Lin,Zhou Yifa,Fan Yuying
Insufficient pancreatic β-cell or insulin-producing β-cell are implicated in all types of diabetes mellitus. Our previous studies showed bee pollen polysaccharide RBPP-P improves insulin resistance in type 2 diabetic mice by inhibiting liver fat deposition. However, its potential of regulating β-cell function and integrity is not fully known. Herein, we observed that β-cell proliferation (n = 10), insulin synthesis (n = 5, p = 0.01684) and insulin incretion (n = 5, p = 0.02115) were intensely activated in MIN6 cells when treatment with RBPP-P. In alloxan-induced diabetic mice, oral administration of RBPP-P (n = 10) effectively decreased the blood glucose (p = 0.0326), drink intake (p < 0.001) and urine (p < 0.001). It directly stimulated phosphorylation of p38 (p = 0.00439), ERK (p = 0.02951) and AKT (p = 0.0072) to maintain the islet function and mass. Thus, our data suggest that RBPP-P is a natural compound to regulate β-cell proliferation and function, indicating it might have therapeutic potential against type 1 diabetes.
研究领域:
药理学
·
内分泌学
·
糖尿病研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）