Tissue inhibitor of metalloproteinase-2 inhibits T-cell infiltration and preserves pancreatic β-cell function in an in vitro type 1 diabetes mellitus model

2006 ◽  
Vol 27 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Chris C. Woods ◽  
Krishnan Sundar ◽  
Cynthia Tessler ◽  
Ty W. Lebsack ◽  
Lora Grainger ◽  
...  
Author(s):  
Xiaoyang Lai ◽  
Xuyang Liu ◽  
Xia Cai ◽  
Fang Zou

Type 1 diabetes (T1D) is a chronic autoimmune disease accompanied by the immune-mediated destruction of pancreatic β-cells. In this study, we aimed to explore the regulatory effects of Vitamin D (VD) supplementation on pancreatic β-cell function by altering the expression of bioinformatically identified cathepsin G (CatG) in T1D model mice. A T1D mouse model was established in non-obese diabetic (NOD) mice, and their islets were isolated and purified. Pancreatic mononuclear cells (MNCs) were collected, from which CD4+ T cells were isolated. The levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) in the supernatant of mouse pancreatic tissue homogenate were assessed using ELISA. Immunohistochemistry and TUNEL staining were conducted to evaluate the effects of VD supplementation on pancreatic tissues of T1D mice. The pancreatic beta-cell line MIN6 was used for in vitro substantiation of findings in vivo. VD supplementation reduced glucose levels and improved glucose tolerance in T1D mice. Further, VD supplementation improved pancreatic β-cell function and suppressed immunological and inflammatory reactions in the T1D mice. We documented overexpression of CatG in diabetes tissue samples, and then showed that VD supplementation normalized the islet immune microenvironment through down-regulating CatG expression in T1D mice. Experiments in vitro subsequently demonstrated that VD supplementation impeded CD4+ T activation by down-regulating CatG expression, and thereby enhanced pancreatic β-cell function. Results of the present study elucidated that VD supplementation can down-regulate the expression of CatG and inhibit CD4+ T cell activation, thereby improving β-cell function in T1D.


2017 ◽  
Vol 34 (11) ◽  
pp. 1521-1531 ◽  
Author(s):  
P. Narendran ◽  
N. Jackson ◽  
A. Daley ◽  
D. Thompson ◽  
K. Stokes ◽  
...  

Author(s):  
Bishnu K Khand ◽  
Ramesh R Bhonde

: Pluripotent Stem Cells [PSCs] are emerging as an excellent cellular source for treatment of many degenerative diseases such as diabetes, ischemic heart failure, Alzheimer’s disease. PSC-derived pancreatic islet β-cells appear to be as a promising therapy for type 1 diabetes patients with impaired β-cell function. Several protocols have been developed to derive β-cells from PSCs. However, these protocols produce β-like cells that show low glucose stimulated insulin secretion [GSIS] function and mirror GSIS profile of functionally immature neonatal β-cells. Several studies have documented a positive correlation between the sirtuins [a family of ageing-related proteins] and the GSIS function of adult β-cells. We are of the view that GSIS function of PSC-derived β-like cells could be enhanced by improving the function of sirtuins in them. Studying the sirtuin expression and activation pattern during the β-cell development and inclusion of the sirtuin activator and inhibitor cocktail [specific to a developmental stage] in the present protocols may help us derive functionally mature, ready-to-use β-cells in-vitro making them suitable for transplantation in type 1 diabetes.


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Olivia McCarthy ◽  
Jason Pitt ◽  
Max L. Eckstein ◽  
Othmar Moser ◽  
Stephen C. Bain ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Ryo Shigemoto ◽  
Takatoshi Anno ◽  
Fumiko Kawasaki ◽  
Kohei Kaku ◽  
Hideaki Kaneto

Type 1 diabetes mellitus (T1DM) is mainly triggered by autoimmune β-cell destruction, usually leading to absolute insulin deficiency. Regarding the speed of β-cell destruction, there are large variations depending on age. In some adult cases, sufficient β-cell function is sometimes retained for a relatively long period and eventually they become dependent on insulin for survival. It is known that even in subjects with T1DM showing high titers of such antibodies, insulin secretory capacity is preserved under several conditions such as “honeymoon” period and slowly progressive T1DM (SPIDDM). Herein, we reported the acute onset T1DM subject with long-term preservation of β-cell function, although his anti-GAD antibody and anti-IA-2 antibody titers were very high for more than 4 years. This case is very important in that his β-cell function was preserved with dipeptidyl peptidase-4 inhibitor alone. This means that there are large variations in the speed of β-cell destruction in the onset of T1DM.


2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110663
Author(s):  
Yucheng Wu ◽  
Yu Lu ◽  
Shufang Yang ◽  
Qingqing Zhang

Aim To assess the effects of incretin-based therapies on β-cell function in patients with type 1 diabetes mellitus (T1DM). Methods We searched the PubMed, Cochrane Library, Embase, and Web of Knowledge databases for eligible randomized clinical trials published up to July 2021. The inclusion criteria were patients with T1DM or latent autoimmune diabetes in adults, patients treated with dipeptidyl peptidase-4 inhibitors or glucagon like peptide-1 receptor agonists, and outcomes included one of the following: fasting plasma glucose, fasting C-peptide, postprandial C-peptide, C-peptide area under the curve (AUC), homeostasis model assessment for β cell function, and insulin resistance. The effects were analyzed using a random effect model with STATA 11.0. Results Eight trials including 427 participants were included in the final analysis. A pooled analysis found no significant difference in fasting plasma glucose, fasting C-peptide, postprandial C-peptide, or C-peptide AUC between patients treated with incretin-based therapies and placebo. The two trials that reported changes in 2-hour postprandial C-peptide and two of the four trials that reported changes in C-peptide AUC reported increases after incretin-based therapies. Conclusion This meta-analysis showed that incretin-based therapies did not preserve β-cell function in patients with T1DM.


2006 ◽  
Vol 23 (8) ◽  
pp. 920-923 ◽  
Author(s):  
D. Pitocco ◽  
A. Crino ◽  
E. Di Stasio ◽  
S. Manfrini ◽  
C. Guglielmi ◽  
...  

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