Related Experiment Video

Updated: Jun 10, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice

Young Sun Kang1, Mi Hwa Lee, Hye Kyoung Song

  • 1Division of Nephrology, Department of Internal Medicine, Korea University, Ansan City, Korea.

Kidney International
|August 6, 2010
PubMed

Insights

Blocking C-C chemokine receptor 2 (CCR2) with RS504393 improved insulin resistance and diabetic nephropathy in mice. This pathway modulation restored kidney function and improved metabolic health in type 2 diabetes.

Area of Science:

  • Nephrology
  • Endocrinology
  • Immunology

Background:

  • Diabetic nephropathy is a complication of diabetes characterized by inflammation.
  • Chemokine ligand 2 (CCL2) and its receptor C-C chemokine receptor 2 (CCR2) pathway contribute to tissue inflammation.
  • Blocking the CCL2/CCR2 pathway may offer therapeutic benefits in diabetic nephropathy.

Purpose of the Study:

  • To investigate the protective mechanisms of a CCR2 antagonist (RS504393) against insulin resistance and diabetic nephropathy.
  • To elucidate the effects of CCR2 antagonism on adipose tissue and renal function in a mouse model of type 2 diabetes.

Main Methods:

  • Utilized db/db mice, a model for type 2 diabetes and obesity.
  • Administered RS504393, a specific CCR2 antagonist.
  • Assessed insulin resistance using biomarkers like HOMA-IR and plasma insulin.
  • Evaluated renal function through urinary albumin excretion and kidney histology.
  • Analyzed adipose tissue morphology and inflammatory markers.

Main Results:

  • RS504393 treatment significantly improved insulin resistance and lipid abnormalities.
  • Antagonist administration reduced epididymal fat mass and altered adipocyte phenotype.
  • Decreased CCL2 expression and lipid hydroperoxide levels were observed in adipose tissue.
  • RS504393 markedly reduced urinary albumin excretion, mesangial expansion, and pro-inflammatory/pro-fibrotic cytokine synthesis.
  • Improved renal lipid metabolism and reduced oxidative stress markers (8-isoprostane) in the kidneys.

Conclusions:

  • CCR2 antagonists can ameliorate insulin resistance through adipose tissue modulation.
  • Blocking the CCR2 pathway restores renal function in type 2 diabetic mice.
  • Therapeutic strategies targeting CCR2 may offer benefits for diabetic nephropathy by addressing both metabolic and fibrotic aspects.

More Related Videos

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy08:47

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

Related Concept Videos

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: Type 2 and Gestational01:22

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
Carbohydrate Metabolism01:36

Carbohydrate 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...
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...
Diabetic Nephropathy01:28

Diabetic 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...