GASTROINTESTINAL PEPTIDES IN GLUCOSE REGULATION

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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. Recent research findings have implicated several gastrointestinal (GI) peptides in the development of type 2 diabetes. In addition, manipulation of GI peptides may prove to be an effective means of treating and preventing the disorder. In particular, the modulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and ghrelin concentrations have been shown to be effective in treating glucose intolerance or type 2 diabetes in rodent models. Moreover, the striking resolution of type 2 diabetes following roux-en Y gastric bypass surgery in humans has been attributed to the alterations in these peptides. Thus, these observations suggest that simultaneous manipulation of two or more of these GI peptides may provide new treatment modalities for type 2 diabetes. Hence, the development of animal models to study the effects of gastric bypass surgery and GI peptides on glucose metabolism is a high priority in diabetes research. Given, the large blood volumes that can be safely attained, the baboon represents a strong candidate for such a model. However, a clearer understanding of normal baboon GI peptide physiology will be an important initial step. The current Southwest National Primate Center pilot study will determine normal GLP-1, GIP, PYY, and ghrelin responses to an intestinal glucose challenge in ten adult male baboons. It is hypothesized that the responses observed in baboons will be similar to those of humans, i.e. increases in GLP-1, GIP, and PYY concentrations and a decrease in ghrelin concentrations. These data will be used in the design of future infusion protocols to assess the synergistic or antagonistic effects of these peptides on glucose metabolism. In addition, these data will help to determine the utility of the baboon as a model for studying the effects of GI peptide alteration resulting from gastric bypass surgery.