Related Experiment Video

Updated: Aug 30, 2026

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes
12:12

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes

Published on: June 16, 2011

Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes

Irina Apostolou1, Zhenyue Hao, Klaus Rajewsky

  • 1Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

The Journal of Experimental Medicine
|October 8, 2003
PubMed

Insights

Fas-dependent apoptosis is not essential for pancreatic beta cell destruction in type 1 diabetes. Fas-deficient mice developed autoimmune diabetes, indicating alternative cell death pathways are involved in this autoimmune disease.

Area of Science:

  • Immunology
  • Endocrinology
  • Cell Biology

Background:

  • Type 1 diabetes involves autoimmune T cell destruction of pancreatic beta cells via largely unknown mechanisms.
  • Previous studies in nonobese diabetic (NOD) mice suggested a role for Fas, but its essentiality remained unclear due to potential pleiotropic functions.

Purpose of the Study:

  • To directly test whether the Fas receptor is an essential mediator of beta cell death in type 1 autoimmune diabetes.
  • To investigate the role of Fas-dependent apoptosis in the pathogenesis of type 1 diabetes.

Main Methods:

  • Generated beta cell-specific Fas gene knockout mice in a transgenic model of type 1 autoimmune diabetes.
  • Utilized CD4+ T cells with a transgenic TCR specific for influenza hemagglutinin (HA) to induce diabetes.
  • Mice expressed HA under the control of the rat insulin promoter.

Main Results:

  • Fas-deficient mice developed autoimmune diabetes.
  • The kinetics of diabetes development in Fas-deficient mice were slightly accelerated compared to controls.
  • This indicates Fas-dependent apoptosis is dispensable for beta cell death in this model.

Conclusions:

  • Fas-dependent apoptosis is not a critical pathway for beta cell destruction in type 1 autoimmune diabetes.
  • Alternative mechanisms contribute to beta cell death in the pathogenesis of type 1 diabetes.
  • These findings clarify the role of Fas in autoimmune diabetes pathogenesis.

More Related Videos

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model11:31

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model

Published on: August 16, 2019

Related Concept Videos

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...
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...
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...
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Diabetes Mellitus: Introduction01:26

Diabetes Mellitus: Introduction

Diabetes mellitus consists of chronic metabolic disorders characterized by persistent hyperglycemia. This elevated blood glucose results from defects in insulin secretion, impaired insulin action, or both. Insulin, produced by pancreatic β-cells, is essential for maintaining glucose homeostasis by facilitating cellular glucose uptake for energy or storage. Disruptions in insulin production or function lead to glucose accumulation in the bloodstream, causing the clinical features and long-term...
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.