The long term goal is to develop and exploit a new animal model for studying hyperphagia and high metabolic rate. As exemplified by the role of the squid axon in the development of our understanding of excitable membranes, rapid progress in biomedical research is most easily achieved by studying a phenomenon in a species exhibiting that phenomenon to an extreme degree, or in experimentally convenient form. This project seeks the equivalent of a squid axon for the fields of gastroenterology, nutrition, and metabolism. Humans and other mammals exhibit many important regulatory responses to the arrival of food in the gut. Nevertheless, these responses are modest in magnitude and can be difficult to study in the usual laboratory mammal models such as rats, because the guts of humans and most other mammals are adapted to frequent small meals and are rarely empty or at rest. Relatively enormous responses, much easier to study, are instead observed in some snake species adapted to infrequent enormous meals. Hence the specific aims of this proposal are to utilize such a species, the Burmese python, as a model of hyperphagia and high metabolic rates.
The first aim i s to establish the experimental conditions (meal size and time after feeding) when python regulatory responses are largest. The remaining aims will be, under those conditions, to identify luminal, hormonal and other signals underlying gastrointestinal responses to feeding, to identify molecular mechanisms and signals for regulation of the intestinal brush-border glucose transporter, and to obtain tissues with maximal amounts of python peptide hormones for isolation and sequencing.
