Background: The enteroendocrine K- and L-cells are responsible for secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon like-peptide 1 (GLP-1), while pancreatic α-cells are responsible for secretion of glucagon. In rodents and humans, dysregulation of the secretion of GIP, GLP-1 and glucagon is associated with impaired regulation of metabolism. This study evaluates the consequences of acute removal of Gip or Gcg expressing cells on glucose metabolism. Methods: Generation of the two diphtheria-toxin-receptor-cellular knock-out mice, TgN(GIP.DTR) and TgN(GCG.DTR) allowed us to study effects of acute ablation of K-cells and L- and α-cells. Results: Diphtheria toxin administration reduced expression of Gip and content of GIP in the proximal jejunum in TgN(GIP.DTR) and expression of Gcg and content of proglucagon derived peptides in both proximal jejunum and terminal ileum as well as content of glucagon in pancreas in TgN(GCG.DTR) compared with wild-type mice. GIP response to oral glucose was attenuated following K-cell loss, but oral and intraperitoneal glucose tolerances were unaffected. Intraperitoneal glucose-tolerance was impaired following combined L- and α-cell loss and normal following α-cell loss. Oral glucose tolerance was improved following L- and α-cell loss, and supernormal following α-cell loss. Conclusion: We present two mouse models allowing studies of effects of K-cell or L- and α-cell loss as well as isolated α-cell loss. Our findings show that intraperitoneal glucose-tolerance is dependent on an intact L-cell mass and underscore the diabetogenic effects of α-cell signaling. Furthermore, the results suggest that K-cells are less involved in acute regulation of mouse glucose metabolism than L- and α-cells.
- enteroendocrine cells
- Copyright © 2012, American Journal of Physiology - Endocrinology and Metabolism