Endothelial Transcytosis of Insulin: Does It Contribute to Insulin Resistance? Warren L. Lee and Amira Klip 10 AUG 2016 https://doi.org/10.1152/physiol.00010.2016insulin must exit capillaries, which (in tissues like skeletal muscle and fat) are lined by a layer of continuous endothelium. Insulin must therefore pass between endothelial cells (paracellular diffusion, green arrow) or be transported across individual cells by transcytosis (red arrow) to access the interstitium.
In the human body, glucose uptake is accomplished via two mechanisms, insulin mediatedglucose uptake (IMGU), which occurs only in insulin-sensitive tissues (i.e. liver, muscle and adipocytes) and non-insulin mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and non-insulin-sensitive tissues (i.e., brain, blood cells, nerve, etc.).
GLUT1 is insulin-independent and is widely distributed in different tissues. GLUT4 is insulin-dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions.
GLUTs 1, 3, and 4 are transporters that have high affinity for glucose ranging in Km of 2–5 mM glucose. Consequently, the functions of these transporters align with the physiological concentration of glucose of about 5 mM. On the other hand, GLUT2 has a low affinity for glucose with its Km of about 15–20 mM glucose. GLUT2, therefore, is able to move glucose into the liver cell and the pancreatic beta cell in proportion to the plasma level of glucose.
An auxiliary function of some GLUTs in the liver seems to be the transport of dehydroascorbic acid (DHA), the oxidized form of ascorbic acid (AA, vitamin C) as described for the GLUT isoforms GLUT1, GLUT3, and GLUT4 [188]. The last-mentioned glucose transporter GLUT4 is known as major isoform in muscular and adipose tissues and only shows minor expression levels in the liver as well [228].
GLUT-2 (SLC2A2) also transports other dietary sugars such as galactose, mannose and fructose with a high affinity for glucosamine[11,24,25]. GLUT-2 is highly expressed in the liver, pancreatic beta cells, and on the basolateral surface of kidney and small intestine epithelia[26,27] with expression regulated by sugars and hormones[23,28].
