Box 112 Biochemistry In Medicine

Defective Glucose and Water Transport in Two Forms of Diabetes

When ingestion of a carbohydrate-rich meal causes blood glucose to exceed the usual concentration between meals (about 5 mM), excess glucose is taken up by the myocytes of cardiac and skeletal muscle (which store it as glycogen) and by adipocytes (which convert it to triacylglycerols). Glucose uptake into myocytes and adipocytes is mediated by the glucose transporter GLUT4. Between meals, some GLUT4 is present in the plasma membrane, but most is sequestered in the membranes of small intracellular vesicles (Fig. 1). Insulin released from the pancreas in response to high blood glucose triggers the movement of these intra-cellular vesicles to the plasma membrane, where they fuse, thus exposing GLUT4 molecules on the outer surface of the cell (see Fig. 12-8). With more GLUT4 molecules in action, the rate of glucose uptake increases 15-fold or more. When blood glucose levels return to normal, insulin release slows and most GLUT4 molecules are removed from the plasma membrane and stored in vesicles.

In type I (juvenile onset) diabetes mellitus, the inability to release insulin (and thus to mobilize glucose transporters) results in low rates of glucose uptake into muscle and adipose tissue. One consequence is a prolonged period of high blood glucose after a carbohydrate-rich meal. This condition is the basis for the glucose tolerance test used to diagnose diabetes (Chapter 23).

The water permeability of epithelial cells lining the renal collecting duct in the kidney is due to the presence of an aquaporin (AQP-2) in their apical plasma membranes (facing the lumen of the duct). Antidiuretic hormone (ADH) regulates the retention of water by mobilizing AQP-2 molecules stored in vesicle membranes within the epithelial cells, much as insulin mobilizes GLUT4 in muscle and adipose tissue. When the vesicles fuse with the epithelial cell plasma membrane, water permeability greatly increases and more water is reabsorbed from the collecting duct and returned to the blood. When the ADH level drops, AQP-2 is resequestered within vesicles, reducing water retention. In the relatively rare human disease diabetes insipidus, a genetic defect in AQP-2 leads to impaired water reabsorption by the kidney. The result is excretion of copious volumes of very dilute urine.

Insulin %

When insulin interacts with its receptor, vesicles move to surface and fuse with the plasma membrane, increasing the number of glucose transporters in the plasma membrane.

Plasma membrane

Insulin receptor

Glucose transporters "stored" within cell in membrane vesicles.

Glucose transporter

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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