INSULIN RESISTANCE IN THE ISLETS OF LANGERHANS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Carbohydrate metabolism involves the utilization of glucose in the body, much of it driven by insulin. Insulin is produced in the islet cells in the pancreas. Insulin helps to keep the level of glucose in our blood at a relatively stable level, so that despite us eating large amounts of carbohydrates in a normal diet, our blood glucose levels stay in the normal range. People who produce enough insulin to maintain normal blood glucose levels are called Normal Glucose Tolerant (NGT). Some people whose bodies are resistant to insulin i.e. insulin is not as effective for them, need to make more insulin to maintain the same blood glucose level as NGT people. They usually have a slightly higher than normal blood glucose level and are termed Impaired Glucose Tolerance (IGT). They do not have diabetes and as per current standards, do not receive treatment. However, they have a 3-9% risk per year of developing Type 2 diabetes. They are therefore at a higher than normal risk for developing diabetes. The next category of abnormal carbohydrate metabolism involves people who have diabetes. These people have high blood glucose levels even though their body produces as much insulin as it can. They need treatment and are treated with insulin and various oral medications, one of which, is a class of drugs known as thiozolidinediones (TZD). These drugs are known as insulin sensitizer. This project will try and prove that resistance at the level of the islet cells plays a role in the development of IGT and diabetes, i.e., if we use a TZD, such a pioglitazone, which is known to enhance sensitivity to insulin, it should also make our islet cells, which produce insulin, more sensitive to it. The more sensitive these cells are to insulin, the more insulin they will produce. This will allow these people to maintain their blood glucose levels in the normal range. If this theory is proven to be true, then it might provide another reason to start treating people with IGT with such insulin sensitizing drugs in an attempt to delay the development of diabetes in these people.