Endocrine Abstracts

High-protein diets (HPDs) improve glucose tolerance. One possible mechanism is through the stimulation of the gut hormone glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L-cells in the gut in response to the amino acid products of protein digestion. The secreted GLP-1 can then act on the GLP-1 receptor (GLP-1R) on the pancreatic β-cell to increase insulin release and improve glucose tolerance. The Pdx1CreERT/GLP-1R fl/fl mouse line, characterised by knockout of GLP-1R in duodenal homeobox 1 (Pdx1)-expressing pancreatic β-cells after tamoxifen induction, was created by crossing over the tamoxifen-inducible Pdx1-Cre/Esr1 mice (Jax 024968) with GLP-1R fl/fl mice (kindly provided by Professor Randy Seeley, University of Michigan). The impact of amino acids on intraperitoneal glucose tolerance and insulin secretion was assessed in mice both before and after GLP-1R knockout from the β-cell. Additionally, ileal mouse organoids were utilised to examine how alanine influences GLP-1 secretion and the involvement of SLC38A2 in this process. We investigated the role of GLP-1 in mediating the effects of ingested protein and of alanine, an amino acid produced by protein digestion thought to play a key role in metabolism. Whey-induced improvements in glucose tolerance and insulin secretion were attenuated in mice with GLP-1R knocked out in β-cells compared to mice with intact GLP-1R. Similarly, the effects of alanine on glucose tolerance and insulin secretion were also blunted in mice with GLP-1R knocked out in β-cells. These results suggest that GLP-1 signalling in the pancreatic β-cell is at least partially responsible for mediating the beneficial effects of whey and alanine on glucose tolerance via an insulin-dependent pathway. Exploiting this system may facilitate dietary approaches to the prevention and treatment of type 2 diabetes.