Recent studies into the physiology of the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have added stimulation of ␤-cell growth, differentiation, and cell survival to well-documented, potent insulinotropic effects. Unfortunately, the therapeutic potential of these hormones is limited by their rapid enzymatic inactivation in vivo by dipeptidyl peptidase IV (DP IV). Inhibition of DP IV, so as to enhance circulating incretin levels, has proved effective in the treatment of type 2 diabetes both in humans and in animal models, stimulating improvements in glucose tolerance, insulin sensitivity, and ␤-cell function. We hypothesized that enhancement of the cytoprotective and ␤-cell regenerative effects of GIP and GLP-1 might extend the therapeutic potential of DP IV inhibitors to include type 1 diabetes. For testing this hypothesis, male Wistar rats, exposed to a single dose of streptozotocin (STZ; 50 mg/kg), were treated twice daily with the DP IV inhibitor P32/98 for 7 weeks. Relative to STZ-injected controls, P32/98-treated animals displayed increased weight gain (230%) and nutrient intake, decreased fed blood glucose (ϳ26 vs. ϳ20 mmol/l, respectively), and a return of plasma insulin values toward normal (0.07 vs. 0.12 nmol/l, respectively). Marked improvements in oral glucose tolerance, suggesting enhanced insulin secretory capacity, were corroborated by pancreas perfusion and insulin content measurements that revealed two-to eightfold increases in both secretory function and insulin content after 7 weeks of treatment. Immunohistochemical analyses of pancreatic sections showed marked increases in the number of small islets (؉35%) and total ␤-cells (؉120%) and in the islet ␤-cell fraction (12% control vs. D espite substantial advances in our understanding of type 1 diabetes, diagnosis of the condition still carries with it a sentence of lifelong daily insulin injection, a partially effective therapy at best (1). New therapeutic strategies under investigation include islet transplantation (and associated stem cell-derived and xenogeneic islet technologies necessary for treatment en masse), the development of improved insulin analogues and delivery systems, gene therapy, and the search for novel agents able to protect and/or stimulate the proliferation and regeneration of islet ␤-cells (1). The importance of the latter strategy is underscored by the need for an inexpensive, benign, preventive therapy that lacks the considerable profile of side effects of most therapies studied to date (e.g., immunosuppressants).A number of recent studies have highlighted the role of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in ␤-cell function and development (2,3). Together, the incretins are responsible for Ͼ50% of nutrient-stimulated insulin release and make up the endocrine arm of the enteroinsular axis (4). Apart from their insulinotropic role, GIP and GLP-1 have been shown to enhance ␤-cell glucose competence and, ...

To provide a sound basis for modification of our paediatric residency education programme, we surveyed graduates from the past 16 years. The questionnaire was designed to determine the adequacy of training rotations in preparing graduates for their career paths. Questionnaires were mailed to 81 graduates; 73 (90%) replied. A modified version was completed by 27 of 29 current residents (93%). For most rotations, responses were normally distributed. However, 10 or more respondents identified exposure in one area as 'excessive' and in 6 as 'inadequate'. Current residents scored many rotations as 'inadequate', likely indicative of their limited exposure to actual practice. Recommendations were consistent for subjects needing more instruction. All major issues raised by graduates had been identified by faculty, but the substantiation enabled changes to be made with widespread support. We recommend periodic survey of graduates to evaluate how well education is preparing residents for their ultimate career paths.

No abstract