The Molecular Basis of Insulin Resistance

Colin Chambersbiology, cells, diabetes, insulin resistance, obesity, pre-diabetes, weight loss Leave a Comment

In answering a forum post on insulin sensitivity I found these articles. They are pretty heavy going but they also get to the nitty gritty of the issue and explain specifically how glut 4 is an important insulin receptor inthe body and how it works.

This article from 2001 explains how the disruption of the GLUT 4 mechanism can affect glucose transport inside skeletal muscle. I feel it may be a few years old, all the references are of 1999 so the current knowledge may have moved on but I wanted to record it here as an interesting report on glut 4 and other insulin receptors.

Further reference

  • Regulation of glucose transport by insulin: traffic control of GLUT4
    • The glucose transporter GLUT4 facilitates insulin-stimulated glucose uptake into muscle and adipose tissue. Defects in glucose uptake represent an early step in the development of type 2 diabetes mellitus.
    • GLUT4 is distributed between the plasma membrane, the trans-Golgi network (TGN), endosomes and small heterogeneous vesicles that consist of sorting intermediates of the endosomal system and GLUT4 storage vesicles (GSVs). Treatment of muscle or adipose cells with insulin stimulates exocytosis of GLUT4 from multiple intracellular compartments, which results in increased GLUT4 levels at the plasma membrane for shuttling of glucose into the cell.
    • In the absence of insulin, at least 50% of GLUT4 is sequestered in specialized immobile GSVs. Stimulation with insulin results in regulated exocytosis of GSVs.
    • GSV mobilization, targeting and fusion at the plasma membrane requires coordinated control of the trafficking machinery by insulin. Trafficking proteins that are regulated by insulin include multiple small GTPases of the RAB, RAL and RHO families, molecular motor proteins, the exocyst complex and SNARE regulatory proteins.
    • Total internal reflection fluorescence microscopy (TIRFM) studies performed in live adipocytes have helped to elucidate the mechanisms by which insulin regulates specific trafficking proteins during GLUT4 exocytosis.
  • Physiology, Glucose Transporter Type 4 GLUT4 exists in skeletal muscle cells, adipocytes, and cardiomyocytes.  It is principally responsible for insulin-stimulated glucose uptake into muscle and adipose cells.  Approximately 80% of glucose gets transported into muscle cells. GLUT4’s glucose-transport system can be upregulated to meet elevated transport demands, such as during times of elevated blood glucose during a carbohydrate-containing meal, or during exercise when skeletal muscles have increased metabolic demand.

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