INSULIN, GLUCAGON AND DIABETES MELLITUS
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10-01-2011, 01:40 PM
Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of 5808 Da.
It is produced in the islets of Langerhans in the pancreas. The name comes from the Latin insula for "island".
Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer.
First isolated from the pancreas in 1922 by Banting and Best, to treat diabetes.
Historically, insulin has been associated with “blood sugar,” so it has profound effects on carbohydrate metabolism.
Besides it also cause abnormality in fat metabolism resulting in conditions like acidosis and arteriosclerosis, that are the usual causes of death in diabetic patient.
Also patients with prolonged diabetes, has diminished ability to synthesize proteins leads to wasting of tissues and many cellular function disorders.
Therefore, it is clear that insulin affects fat and protein metabolism almost as much as it dose carbohydrate metabolism.
CHEMISTRY AND SYNTHESIS
Insulin is a small protein; human insulin has a mol wt. of 5808 Da.
It is composed of two amino acid chains, connected to each other by disulphide linkages.
When the two amino acid chains are split apart, the functional activity of the insulin molecule is lost.
Insulin is synthesized in the beta cells by the usual cell machinery for protein synthesis.
Beginning with translation of insulin RNA by ribosomes attached to the endoplasmic reticulum to form an insulin preprohormone.
This initial preprohormone has a mol wt. of about 11,500, but it is then cleaved in the endoplasmic reticulum to form a proinsulin with a mol wt. of about 9000 Da
Most of this further cleaved in the golgi apparatus to form insulin and peptide fragments before being pakaged in the secretory granules.
About 1/6th of the final secretory product is still in the form of proinsulin which has no insulin activity.
Glucagon is a hormone, secreted by the pancreas, that raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels.
The pancreas releases glucagon when blood glucose levels fall too low.
Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream.
Glucagon also stimulates the release of insulin, so that glucose can be taken up and used by insulin-dependent tissues.
Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels at the right level.
Diabetes mellitus, often simply referred to as diabetes—is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).
There are three main types of diabetes:
Type 1 diabetes: results from the body's failure to produce insulin, and presently requires the person to inject insulin. (Also referred to as insulin-dependent diabetes mellitus, IDDM for short, and juvenile diabetes.)
Type 2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.
Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.
Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.
Acute complications include hypoglycemia, diabetic ketoacidosis, or nonketotic hyperosmolar coma. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage.
Adequate treatment of diabetes is thus important, as well as blood pressure control and lifestyle factors such as smoking cessation and maintaining a healthy body weight.
As of 2000 at least 171 million people worldwide suffer from diabetes, or 2.8% of the population. Type 2 diabetes is by far the most common, affecting 90 to 95% of the U.S. diabetes population.
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