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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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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.
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Updated: Dec 11, 2025

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion
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Immunoglobulins G modulate endothelial function and affect insulin sensitivity in humans.

Raffaele Napoli1, Antonio Ruvolo1, Paola Triggianese1

  • 1Department of Translational Medical Sciences, Federico II University School of Medicine, Naples, Italy.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|August 19, 2020
PubMed
Summary

Low immunoglobulin G (IgG) levels are linked to endothelial dysfunction. Intravenous IgG (IVIgG) therapy improved endothelial function and insulin sensitivity in CVID patients, suggesting a protective role against atherosclerosis.

Keywords:
AtherosclerosisEndothelial functionFlow mediated dilationImmunoglobulinsInsulin resistance

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Area of Science:

  • Immunology
  • Cardiovascular Medicine
  • Metabolic Disorders

Background:

  • Animal studies suggest immunoglobulins G (IgG) contribute to atherosclerosis and diabetes via endothelial dysfunction and insulin resistance.
  • Patients with common variable immunodeficiency (CVID) have low IgG levels and receive intravenous IgG (IVIgG) therapy, offering a human model to study IgG's role.
  • This study investigates whether circulating IgG influences human endothelial function and insulin sensitivity.

Purpose of the Study:

  • To determine the effect of intravenous IgG (IVIgG) on endothelial function in patients with common variable immunodeficiency (CVID).
  • To assess the impact of IVIgG on insulin sensitivity in CVID patients.
  • To explore the in vitro effect of IgG on nitric oxide production in endothelial cells.

Main Methods:

  • Compared endothelial function (flow-mediated dilation, FMD) and insulin sensitivity (HOMA-IR) in 24 CVID patients and 17 healthy controls.
  • Measured FMD, plasma glucose, and insulin levels at baseline and at multiple time points after IVIgG infusion in CVID patients.
  • Investigated the effect of human IgG on nitric oxide (NO) production in human coronary artery endothelial cells (HCAEC) in vitro.

Main Results:

  • CVID patients exhibited significantly impaired FMD at baseline compared to controls.
  • IVIgG infusion transiently improved FMD in CVID patients, normalizing levels at 1 and 7 days post-infusion.
  • Serum insulin concentration and HOMA-IR index decreased by 50% after IVIgG infusion in CVID patients.
  • In vitro, IgG stimulated NO production in HCAEC.

Conclusions:

  • Reduced IgG levels are associated with endothelial dysfunction.
  • IVIgG therapy directly enhances endothelial function and improves insulin sensitivity.
  • Human IgG may possess anti-atherogenic properties, potentially through direct effects on endothelial cells and NO production.