This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this proposal is to perform the insulin suppression test (IST) in 20 subjects to gain experience and train our staff. The IST is a physiologic study that involves simultaneous infusion of glucose, insulin, and octreotide for 3 hours. During the IST, glucose and insulin levels reach steady state levels; these allow direct quantification of insulin resistance and insulin clearance. These are traits that we will be examining in future research studies. This pilot study will facilitate our grant efforts by demonstrating that we have the ability to perform the IST.Insulin is the hormone that allows muscle and fat tissue to absorb sugar (glucose) from the bloodstream for use as fuel or storage. Insulin is best-known for its role in diabetes mellitus, wherein a deficiency of insulin action leads to very high levels of glucose in the blood and damage to eyes, kidneys, nerves and an increased risk of cardiovascular disease.A defect in insulin s ability to promote glucose uptake is called insulin resistance. The body compensates for insulin resistance by increasing the amount of insulin secreted from the pancreas, a process called compensatory hyperinsulinemia. Factors that also influence the amount of insulin in the body are insulin secretion and insulin clearance (insulin clearance is the process by which the body eliminates insulin). Insulin resistance and hyperinsulinemia are thought to underlie many conditions besides diabetes. These include obesity, the metabolic syndrome, and polycystic ovary syndrome. All of these are very significant because they are associated with an increased risk of developing diabetes and heart disease. The insulin resistance or metabolic syndrome affects approximately 25% of adults in the U.S., and polycystic ovary syndrome (PCOS) affects 5-7% of reproductive-aged women. Patients with PCOS suffer from defective ovulation and high male hormones called androgens. Long term consequences of this disease are infertility, diabetes, uterine cancer and heart disease. Measurement of insulin resistance is not a simple matter. Simple measurements based on a single blood test assessment of insulin and glucose level are easy to obtain but are imprecise measures of insulin resistance. To more accurately measure insulin resistance for research purposes, more complicated studies are required whereby a study subject undergoes infusion studies over a few hours. The data obtained from such studies can be used to derive very accurate measurements of insulin resistance. Our goal is to establish one such procedure at Cedars-Sinai, to allow researchers to perform studies that critically evaluate insulin-related traits. This procedure is called the Insulin Suppression Test (IST). It involves a simultaneous infusion of glucose, insulin, and the drug somatostatin, over a three-hour period. The levels of glucose and insulin that occur towards the end of the infusion allow calculation of insulin resistance and insulin clearance. We propose to perform the IST on 20 subjects, male or female, lean or obese, and with or without polycystic ovary syndrome, diabetes, or the metabolic syndrome. The experience gained will be utilized in future studies of large numbers of such subjects, testing multiple hypotheses about the impact of insulin in human health and disease.
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