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Related Concept Videos

Type I Diabetes I: Introduction01:12

Type I Diabetes I: Introduction

Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.Autoimmune Destruction of β-CellsThe hallmark of type 1 diabetes is an...
Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Type II Diabetes I: Introduction01:26

Type II Diabetes I: Introduction

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
Type II Diabetes II: Pathophysiology01:24

Type II Diabetes II: Pathophysiology

PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
Diabetes Mellitus: Overview and Type I Subtype01:22

Diabetes Mellitus: Overview and Type I Subtype

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...

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Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
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Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis.

Sanja Glisic1, Parthav Jailwala

  • 1Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America. sglisic@mcw.edu

Plos One
|May 8, 2012
PubMed
Summary

Regulatory T cells (Tregs) undergo increased apoptosis in early Type 1 Diabetes (T1D), influenced by HLA risk and inflammation. Understanding these pathways may personalize T1D prevention strategies.

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Area of Science:

  • Immunology
  • Endocrinology
  • Genetics

Background:

  • Previous studies showed increased regulatory T cell (Treg) apoptosis in recent-onset Type 1 Diabetes (T1D) and autoantibody-positive (Ab+) individuals.
  • This apoptosis was linked to High HLA risk and decreased during the T1D honeymoon period cessation.

Purpose of the Study:

  • To comprehensively assess T-cell changes during T1D pathogenesis using integrated approaches.
  • To investigate Treg apoptosis, function, surface markers, HLA class II gene expression, and the influence of HLA risk.

Main Methods:

  • Genetics, genomics, functional cell-based assays, and flow cytometry were employed.
  • Ex vivo Treg apoptosis and function, surface markers, HLA class II gene expression, and apoptosis-related gene contributions were measured.

Main Results:

  • High HLA risk healthy controls showed increased Treg apoptosis and FADD overexpression.
  • Tregs in recent-onset T1D subjects during the honeymoon phase died via growth hormone withdrawal, oxidative stress, mitochondrial pathways, and TNF-receptor family members.
  • Ab+ subjects exhibited high inflammation contributing to Treg apoptosis, alongside other activated pathways.

Conclusions:

  • T1D progression is linked to increased Treg apoptosis coupled with decreased Treg function.
  • Distinct apoptotic pathways are involved in Treg loss across different T1D stages and risk groups.
  • Findings suggest potential for stage-specific preventive treatments for T1D based on Treg apoptosis and function.