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Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.
Diabetologia
November 2024
Department of Medicine, Division of Nutritional Sciences and Obesity Research, Washington University School of Medicine, St Louis, MO, USA.
Article Synopsis
- Microvascular dysfunction contributes to insulin resistance, particularly in individuals with a genetic variant (G allele) that reduces CD36 expression, impacting blood vessel function and glucose disposal.* -
- Through various experimental methods, the study found that while CD36-deficient mice and humans showed improved insulin-stimulated glucose disposal, they had issues with blood volume response and vascular compliance, indicating a paradoxical relationship between microvascular resistance and insulin sensitivity.* -
- The findings suggest that while CD36 deficiency may enhance glucose disposal efficiency, it simultaneously hampers the microvasculature's response to insulin, affecting oxygen delivery and energy metabolism in muscle and heart tissues.*
Plasma volume response patterns and a physiologic model of ultrafiltration in hemodialysis.
Artif Organs
September 2024
Manchester Academy of Health Sciences Centre, Manchester University Hospitals, Manchester, UK.
Background: Ultrafiltration (UF) is an essential process of restoring fluid homeostasis during hemodialysis (HD). Fluid shifts across the extracellular compartments during UF, predominantly across the capillary interface and between the macro- and microcirculation. A mismatch between UF and transcapillary fluid transport can lead to hemodynamic instability leading to cardiac morbidity.
View Article and Find Full Text PDFThis microfluidic-optical fiber sensor is an experimental system designed to transport and monitor 3D cell cultures, facilitating medical research and technology. This system includes a photonic crystal fiber with a hollow core diameter of 22 µm, which functions as a bridge between two microfluidic devices. The purpose of this system was to transport 3T3 cells (of diameters from 15 µm to 23 µm) between the two devices.
View Article and Find Full Text PDFMathematical model of oxygen, nutrient, and drug transport in tuberculosis granulomas.
PLoS Comput Biol
February 2024
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Physiological abnormalities in pulmonary granulomas-pathological hallmarks of tuberculosis (TB)-compromise the transport of oxygen, nutrients, and drugs. In prior studies, we demonstrated mathematically and experimentally that hypoxia and necrosis emerge in the granuloma microenvironment (GME) as a direct result of limited oxygen availability. Building on our initial model of avascular oxygen diffusion, here we explore additional aspects of oxygen transport, including the roles of granuloma vasculature, transcapillary transport, plasma dilution, and interstitial convection, followed by cellular metabolism.
View Article and Find Full Text PDFMonoclonal Antibody Pharmacokinetics in Cynomolgus Monkeys Following Subcutaneous Administration: Physiologically Based Model Predictions from Physiochemical Properties.
AAPS J
December 2022
Department of Biomedical Engineering, University of Southern California, Los Angeles, California, 90089, USA.
An integrated physiologically based modeling framework is presented for predicting pharmacokinetics and bioavailability of subcutaneously administered monoclonal antibodies in cynomolgus monkeys, based on in silico structure-derived metrics characterizing antibody size, overall charge, local charge, and hydrophobicity. The model accounts for antibody-specific differences in pinocytosis, transcapillary transport, local lymphatic uptake, and pre-systemic degradation at the subcutaneous injection site and reliably predicts the pharmacokinetics of five different wild-type mAbs and their Fc variants following intravenous and subcutaneous administration. Significant associations were found between subcutaneous injection site degradation rate and the antibody's local positive charge of its complementarity-determining region (R = 0.
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