scholarly journals Bottom-up proteomics analysis of the secretome of murine islets of Langerhans in elevated glucose levels

The Analyst ◽  
2017 ◽  
Vol 142 (2) ◽  
pp. 284-291 ◽  
Author(s):  
Andrew Schmudlach ◽  
Jeremy Felton ◽  
Robert T. Kennedy ◽  
Norman J. Dovichi
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Oxidative Damage ◽  
Islets Of Langerhans ◽  
High Glucose ◽  
Proteomics Analysis ◽  
Glucose Levels ◽  
Elevated Glucose

Glucotoxicity is a causative agent of type-2 diabetes, where high glucose levels damage the islets of Langerhans resulting in oxidative damage and endoplasmic reticulum stress.

scholarly journals The frequency of Tim-3 on circulating Tfh cells was increased in type 2 diabetes mellitus patients

2020 ◽  
Vol 18 ◽  
pp. 205873922098280
Author(s):  
Shuai Guo ◽  
Xujie Yu ◽  
Limei Wang ◽  
Jing Jing ◽  
Yuanyuan Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Tfh Cells ◽  
Fasting Plasma ◽  
Healthy Donors

Type 2 diabetes mellitus (T2DM) is a chronic, low-grade inflammation disease. T follicular helper (Tfh) cells and T cell immunoglobulin and mucin domain 3 (Tim-3) are implicated in many immune diseases. This study aims to explore whether Tim-3 expression on Tfh cells is associated with T2DM progression. White blood cells (WBCs) were harvested from 30 patients with T2DM and 20 healthy donors. The abundance of circulating Tfh cells (cTfh) and the frequency of Tim-3 were analyzed by flow cytometry. Levels of fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C), and fasting plasma C-peptide were measured. Body mass index (BMI) and diabetes duration were also recorded. Patients with T2DM had higher numbers of cTfh cells. In addition, cTfh cells showed a negative correlation with HbA1C and diabetes duration, a positive correlation with fasting plasma C-peptide. The frequency of Tim-3 on cTfh cells was higher among T2DM patients compared with healthy donors. The in vitro experiment showed that high glucose levels increased the abundance cTfh cells but had no effect on Tim-3 expression. Our results suggest that cTfh cells and associated Tim-3 frequency may contribute to the progression of T2DM, and high glucose levels may influence cTfh cells directly.

scholarly journals Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 395-409 ◽  
Author(s):  
Masaya Oshima ◽  
Séverine Pechberty ◽  
Lara Bellini ◽  
Sven O. Göpel ◽  
Mélanie Campana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Identity ◽  
Human Beta Cells ◽  
Human Beta Cell ◽  
Stearoyl Coa Desaturase

Abstract Aims/hypothesis During the onset of type 2 diabetes, excessive dietary intake of saturated NEFA and fructose lead to impaired insulin production and secretion by insulin-producing pancreatic beta cells. The majority of data on the deleterious effects of lipids on functional beta cell mass were obtained either in vivo in rodent models or in vitro using rodent islets and beta cell lines. Translating data from rodent to human beta cells remains challenging. Here, we used the human beta cell line EndoC-βH1 and analysed its sensitivity to a lipotoxic and glucolipotoxic (high palmitate with or without high glucose) insult, as a way to model human beta cells in a type 2 diabetes environment. Methods EndoC-βH1 cells were exposed to palmitate after knockdown of genes related to saturated NEFA metabolism. We analysed whether and how palmitate induces apoptosis, stress and inflammation and modulates beta cell identity. Results EndoC-βH1 cells were insensitive to the deleterious effects of saturated NEFA (palmitate and stearate) unless stearoyl CoA desaturase (SCD) was silenced. SCD was abundantly expressed in EndoC-βH1 cells, as well as in human islets and human induced pluripotent stem cell-derived beta cells. SCD silencing induced markers of inflammation and endoplasmic reticulum stress and also IAPP mRNA. Treatment with the SCD products oleate or palmitoleate reversed inflammation and endoplasmic reticulum stress. Upon SCD knockdown, palmitate induced expression of dedifferentiation markers such as SOX9, MYC and HES1. Interestingly, SCD knockdown by itself disrupted beta cell identity with a decrease in mature beta cell markers INS, MAFA and SLC30A8 and decreased insulin content and glucose-stimulated insulin secretion. Conclusions/interpretation The present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity. Data availability Microarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code.

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