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Edited by Yimaitong, please do not reprint without authorization
.
Patients with type 1 diabetes need to receive insulin replacement therapy for life
.
However, based on the different responses of pancreatic islet α cells to pancreatic β cells under pressure, this study proposes a new potential idea
.
Research background: Pancreatic islet alpha cells and beta cells exposed to stressors have different outcomes.
A considerable part of type 1 diabetes stems from autoimmune problems and is characterized by progressive loss of pancreatic beta cells
.
During the progression of type 1 diabetes, both pancreatic α cells and β cells are exposed to the same stressor, such as pro-inflammatory cytokines (IL-1β, IFNγ, TNFα, etc.
), but only pancreatic islet α cells survive in this environment Come down
.
The underlying mechanism of this alpha cell resistance has not yet been elucidated
.
At the EASD (European Society for the Study of Diabetes) 2021 annual meeting held on September 28, Laura Marroqui Esclapez, a scholar from Miguel Hernández de Elche University in Spain, shared an article from her The team’s research attempts to identify proteins that are highly expressed in alpha cells and can protect alpha cells from pro-inflammatory cytokines, opening up new ideas for the treatment of type 1 diabetes
.
Laura Marroqui Esclapez Research Method: Identifying Highly Expressed Gene Fragments in Pancreatic Islet α Cells The research team used mouse or human purified islet α and β cell RNA sequencing data from four different studies to conduct unbiased bioinformatics analysis
.
Select candidate genes according to the following selection criteria: ➤Average expression (RPKM)≥2; ➤Expression in α cells ≥2 times of expression in β cells; ➤Genes should be expressed in all samples; ➤Genes should be in the selected four This was confirmed in the RNA sequencing data
.
Measure the corresponding genes in rat α and β cells purified by flow fluorescence sorting and alpha TC1-9 (mouse pancreatic cancer islet α cells) and MIN6 (mouse pancreatic cancer islet β cells) cell lines by RT-PCR Fragment mRNA expression level
.
At the same time, siRNA (small interfering RNA) is used to inhibit gene expression to determine the result of loss or decrease in gene expression, and Hoechst/Propidium staining is used to evaluate cell viability
.
Research results: 4 potential gene fragments.
A total of 25 candidate gene fragments meet the established selection criteria
.
From these 25 gene fragments, four potential gene fragments were screened based on their known functions, namely Itpr1 (1,4,5-inositol triphosphate receptor type 1 gene), Pdk4 (pyruvate dehydrogenation) Enzyme kinase-4 gene), Vim (vimentin gene) and Ttr (transthyretin gene)
.
The mRNA expression of all the above four genes in pancreatic islet α cells was significantly higher than their expression levels in pancreatic β cells (8~266 times; n=4-7; p<0.
05)
.
In the cell line culture, the expressions of Itpr1, Pdk4 and Vim in alpha TC1-9 were all higher than those in MIN6 cells (n=6-12; p<0.
05), while the expression of Ttr in alpha TC1-9 was lower than that in MIN6 cells ( n=7-12; p<0.
05)
.
It is worth noting that in the alpha TC1-9 cell line, the silencing of Itpr1, Pdk4, Vim or Ttr accelerated cell apoptosis (increase by 1.
5 to 3 times; n=3-8, p<0.
05)
.
After exposure to the pro-inflammatory cytokine IL-1β+IFNγ, similar increased apoptosis can still be observed, which means that the expression products of these four gene fragments may be the "secret weapon" of pancreatic islet α against stress
.
Research conclusions The researchers believe that these findings indicate that this bioinformatics analysis method may be an effective method and provide a new research idea for the diagnosis and treatment of type 1 diabetes
.