Related Experiment Video
Updated: Aug 4, 2026
06:27
Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Increasing neutrophil F-actin corrects CD11b exposure in Type 2 diabetes
A Advani1, S M Marshall, T H Thomas
1Department of Medicine, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK. andrew.advani@ncl.ac.uk
European Journal of Clinical Investigation
|May 19, 2004
Summary
In Type 2 diabetes, neutrophils show impaired actin polymerization, affecting CD11b/CD18 integrin function. Increasing actin polymerization can correct this defect, potentially improving diabetic vascular complication outcomes.
Area of Science:
- Immunology
- Cell Biology
- Diabetology
Background:
- Leukocyte dysfunction is implicated in diabetic vascular complications.
- Neutrophil adherence to endothelium involves beta(2)integrin CD11b/CD18.
- Type 2 diabetes is characterized by increased neutrophil CD11b expression and impaired actin polymerization.
Purpose of the Study:
- To investigate if enhanced neutrophil actin polymerization can rectify the defect in CD11b/CD18 integrin exposure in Type 2 diabetes.
- To explore the relationship between actin polymerization and integrin function in diabetic neutrophils.
Main Methods:
- Neutrophil actin polymerization was stimulated using phenylarsine oxide (PAO), a tyrosine phosphatase inhibitor.
- Cytoskeletal phosphotyrosine, F-actin levels (phalloidin-FITC), and surface CD11b expression (anti-CD11b-PE) were quantified via flow cytometry.
- Triton X-100 insoluble fractions were analyzed by immunoblotting.
Main Results:
- PAO increased phosphotyrosine in neutrophils from both Type 2 diabetes patients and controls.
- Neutrophils from Type 2 diabetes patients exhibited impaired F-actin polymerization and CD11b/CD18 surface expression in response to PAO.
- However, higher PAO concentrations (>10 micro mol L(-1)) normalized F-actin levels and corrected CD11b/CD18 down-regulation in diabetic neutrophils.
Conclusions:
- Impaired neutrophil actin polymerization in Type 2 diabetes suggests a downstream defect.
- Restoring actin polymerization above a threshold level corrects the aberrant integrin exposure.
- Targeting actin polymerization defects may offer a therapeutic strategy for diabetic vascular complications.
Related Concept Videos
01:36Carbohydrate Metabolism
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in the...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in the...
01:12Type 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...
01:26Type 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...
01:26Type 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...
01:24Type 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.
01:28Diabetic Nephropathy
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...