Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, MD
8 August 2007

WHAT IS AN INCRETIN? 

            Most people know that there are chemicals in the body called hormones.  A hormone is a messenger chemical sent from one organ of the body to regulate the function of another part of the body.  Common well-known examples include thyroid hormone that is made by the thyroid gland in the neck.  This hormone goes to many different places in the body and regulates energy expenditure.  Another well-known hormone is insulin made by the Islets of Langerhans in the pancreas.  Insulin goes to many different cells in the body and regulates their uptake of sugar.  Hormone function has always been known to be complex.  For instance, insulin works very potently on muscle but has nothing to do with glucose uptake by the brain. 

            For many years, it was thought that insulin secretion was regulated by the blood sugar.  There was a balanced feedback mechanism whereby insulin secretion was stimulated by the  blood sugar going up.  It made perfect sense that this would be a balanced system to regulate the blood sugar in the body.

            But it was known many years ago that if 75 grams of glucose was consumed by drinking, the insulin secretion was much greater than if the same 75 grams of glucose was injected intravenously.  This was very puzzling because the blood sugar with glucose given intravenously goes much higher than does the same amount of sugar when a person drinks it.  Yet the insulin secretion from drinking glucose was much greater. 

            In the 1980s, scientists found a new hormone called GLP (glucagon-like peptide).  This is a hormone secreted by the intestine when a person ate carbohydrates or sugar.  GLP went from the intestine to the pancreas to warn it that there is going to be an increase in blood sugar coming and the pancreas should start making more insulin right away.  When scientists found this hormone they now understood why drinking glucose lead to a higher insulin response than when a person had the same amount of glucose injected into them intravenously. 

            This was a novel observation but not much attention was paid to it until it was recognized that patients with type II diabetes didn’t make much GLP.  It had been known for years that type II diabetics made excessive amounts of insulin, but were simply not sensitive to it.  In spite of all the insulin that a type II diabetic makes, it just doesn’t lower the blood sugar very well due to what is called insulin resistance.  But now here was a new abnormality in which the type II diabetic lacked a normal amount of GLP hormone.  Subsequently, it was found that there was another hormone called GIP that also stimulated the pancreas to make more insulin.  Thus far, these are the only two hormones in the body that have been found to act in this way.  These two hormones are called incretins.  An incretin is a hormone made by the intestine that stimulates the pancreas to make more insulin.

            Why are these hormones important?  The logical answer would be that they help the body make more insulin and without them, whatever insulin deficiency the person has would seem to get worse.  But the absence of an incretin won’t explain why a type II diabetic becomes resistant to the insulin they already have.  The second reason that these incretins are important is that we now have a new medication on the market that will increase the amount of incretin that the person has to use.  This will raise the amount of insulin they can produce and it definitely does better control the blood sugar.  These new medications (Januvia- sitagliptin) have the advantage of not causing fluid retention like Avandia or Actos does.  In addition, these new medications can be used in patients that have kidney problems.  Most of the oral medications available to treat diabetes cannot be used in patients with chronic kidney disease.

            As research in medicine continues, we are learning more and more about hormones that the intestine makes to regulate other body functions.  There is a hormone called cholecystokinin that is secreted by the stomach when a person eats fats.  This hormone tells the gallbladder to empty and mix with the fatty food so it is better digested.  There is a hormone called ghrelin made by the stomach.  As the stomach remains empty for a period of time, this hormone builds up and tells the person to eat and may play a role in obesity.  Drugs to combat ghrelin are being investigated at this time, but none are available on the market yet.  Many other hormones are made by the intestine, but only GIP and GLP are incretins.  So in answer to the question, “What is an incretin?”, an incretin is a hormone made by the intestine that stimulates the pancreas to make more insulin.