Metabolic Disorders from Diabetes Mellitus:
The key defect which leads to diabetes mellitus is the lack
of insulin. Insulin, a polypeptide,
interacts with the cell membrane to assist the entry of glucose
into the cell. In addition, either directly or indirectly,
insulin increases the rate of glycolysis, glycogenesis, lipogenesis,
and the synthesis of protein. Insulin decreases the rate of glycogenolysis
and gluconeogenesis in the liver. In the absence of insulin,
the opposite effects are produced.
Normally, more than 80% of the energy produced by the body
is derived from the combustion of carbohydrates. If carbohydrate
metabolism is severely limited, the cell begins to oxidize fat
reserves for energy. In addition, proteins are degraded to amino
acids which in turn are converted to glucose. If excessive fat
metabolism occurs in conjunction with inadequate carbohydrate
metabolism, there are inadequate amounts of oxaloacetic acid
with which to react with acetyl CoA from the fatty acid spiral.
An excess of acetyl CoA leads to a build up of ketone bodies
leading to ketosis and since ketone bodies are also acids, this
leads to a condition known as acidosis. Severe acidosis, if not
counteracted, can result in coma and death. A diabetic coma is
accompanied by labored breathing, a dry parched mouth and tongue,
acetone on the breath, a rapid pulse, low blood pressure and
often vomiting.The metabolic disorders associated with diabetes
mellitus are summarized in the graphic on the left.
Long term complications of the diabetic condition includes
arteriosclerosis and other cardiovascular circulatory problems,
changes in eye retina and eye cataracts, nervous system problems,
and kidney diseases caused by overwork of removing excess glucose
and water. Gangrene may easily develop as a result of the circulatory
problems mentioned earlier.
Since Type I diabetes mellitus can only be treated with daily
injections of insulin, the amount of insulin must be carefully
regulated. An overdose of insulin may result in insulin shock.
Type II diabetes may be treated with oral drugs such as sulphonureas
such as tolbutamide and chlorpropamide. The principal action
is on beta islet cells, stimulating the secretion of insulin.
These are not insulin substitutes but work by stimulating the
pancreas to secrete insulin.
Biguanides, orally active hypoglycaemic agents, appear to
act by increasing glucose uptake into the tissues. They may also
increase glycolysis and decrease gluconeogenesis.
Troglitazone is an example of a thiazolidine dione which is
an oral drug approved for treating non-insulin dependent diabetes
mellitus. It acts as an insulin sensitiser. It may be used alone
(monotherapy) or in combination with sulphonylureas.