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. Impaired glucose tolerance (IGT) is characterized by beta-cell dysfunction and insulin resistance. Short-term mild hyperglycemia enhances one or both these parameters in normal humans [1, 2]. To determine whether short-term mild hyperglycemia improves beta-cell function and insulin sensitivity in subjects with IGT, we will evaluate the effects of 24-h glucose and saline infusions on these parameters. Furthermore, we will compare these responses in subjects with IGT and subjects with NGT. Beta-cell function and insulin sensitivity will be quantified using a frequently sampled intravenous glucose tolerance test (FSIGTT) and this will be followed by an oral glucose tolerance test (OGTT) to measure the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that play important roles in regulating insulin secretion. The incretin hormone response to a standard meal and change in plasma lipoprotein concentration will also be tested in subjects with IGT or NGT after being exposed to short-term glucose or saline infusion.
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