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Apoptosis and Sorbitol Dehydrogenase in Diabetes

Diabetes mellitus is a chronic disease that occurs either when the pancreas, which secretes digestive enzymes, does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar levels. Increased blood sugar levels (called hyperglycemia) is a common effect of uncontrolled diabetes and over time can lead to complications, including serious organ damage.

  1. Onset of Diabetes

    • Research shows that a short-term increase in blood sugar levels does not cause any health-related problem. People with long-term high blood sugar levels, though, often develop diabetic neuropathy (an abnormal and degenerative state of the nervous system), which tends to alter the usual metabolic pathways in the body. Persistent high levels of blood glucose lead to poor protein synthesis, stress, hyperglycemia, and suppressed appetite.

    Polyol Pathway

    • Diabetes leads to increased levels of glucose in tissues since the tissues are not able to utilize glucose because of a deficiency of insulin. This glucose is converted into sorbitol (a faintly sweet alcohol), which is then converted into fructose. Increased glucose levels trigger the activation of the polyol pathway, in which the enzyme aldose reductase in the presence of co-factor NADPH converts glucose into sorbitol. This sorbitol is further converted into fructose by the action of the sorbitol dehydrogenase enzyme.

    The Relationship between the Polyol Pathway and Diabetic Complications

    • In some diabetic patients, the aldose reductase enzyme is more active than sorbitol dehydrogenase. The combination of this situation results in the formation of sorbitol from glucose that is not further converted into fructose. Hence, sorbitol starts to accumulate in the tissues, mainly in nerves and blood vessels. The metabolism of sorbitol is slower than that of fructose or glucose. Sorbitol is hyper-osmotic, so water accumulates in the tissues, resulting in edema or tissue swelling. The edema interferes with the routine functions of body cells. The malfunctioning of cells normally leads to apoptosis, which is defined as a programmed cell death because of unfavorable living conditions for the cell.

    Oxidant/Antioxidant Levels

    • The aldose reductase pathway or polyol pathway may be implicated in diabetic complications. The enzyme aldose reductase competes with the glutathione peroxidase enzyme for its co-factor NADPH. Glutathione peroxidase is an important enzyme that regulates the delicate balance of oxidant and antioxidants in body. This creates an improper functioning of this enzyme system, so the balance between oxidant and antioxidant levels are disturbed, creating reactive oxygen species (ROS) that act as oxidants. These active oxygen molecules cause damage at cellular levels and may initiate apoptosis.

    Preventing Complications of Diabetes

    • Blood sugar levels are an important parameter for the diagnosis and treatment of a disease. So, it is highly important, especially to those who have been diagnosed with diabetes, to maintain normal sugar levels in the blood. Proper diet and regular exercise help maintain the balance in blood glucose levels. Persistent deviation from the normal range of sugar levels often results in tissue destruction, which damages internal organs such as the kidneys.

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