Peptide YY (PYY) is a gut-derived hormone that is renowned for its effects on satiety. Reduced satiety in obese people has been attributed to low fasting and postprandial PYY levels. However, it has not been determined whether low PYY levels are the cause or the outcome of obesity. Moreover, the long-term role of PYY in regulating energy balance is unclear. Results presented in this thesis, using PYY-deficient mice (PYY-/-) and PYY transgenic mice (PYYtg) highlight that PYY indeed has an important role in regulating energy balance and glucose homeostasis in vivo. PYY knockout mice became obese with ageing or high-fat feeding linked to a hyperinsulinemic phenotype associated with hypersecretion of insulin from isolated pancreatic islets. These findings suggested that PYY deficiency may be a predisposing factor for the development of obesity and type 2 diabetes. On the other hand, PYYtg mice exhibited decreased adiposity and increased metabolism under high-fat feeding. Furthermore, PYYtg/ob mice had improved glucose tolerance and decreased adiposity. These latter studies suggested that high circulating PYY levels may protect against the development of obesity and type 2 diabetes. Interestingly, both animal models support PYY as an important regulator of the somatotropic axis. These preliminary findings prompted investigations in understanding whether low PYY levels may be a predisposing factor for the development of obesity and type 2 diabetes in human subjects. In a population of healthy human subjects that had a predisposition to the development of type 2 diabetes and obesity, fasting PYY levels were lower than in normal subjects. Moreover, low fasting PYY levels strongly correlated with decreased insulin sensitivity and high levels of fasting insulin. Collectively, these findings suggest that low circulating levels of PYY could contribute to increased adiposity, insulin resistance and type 2 diabetes. Therefore determination of PYY levels may be a method of detecting whether people are predisposed to becoming obese and insulin resistant. This work also suggests that treatments that enhance circulating PYY levels may be protective in the development of obesity and type 2 diabetes.
| Identifer | oai:union.ndltd.org:ADTP/215606 |
| Date | January 2007 |
| Creators | Boey, Dana, School of Medicine, UNSW |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://unsworks.unsw.edu.au/copyright, http://unsworks.unsw.edu.au/copyright |
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