We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Gut-specific Neprilysin Deletion Protects Against Fat-induced Insulin Secretory Dysfunction in Male Mice.
- Authors
Esser, Nathalie; Mongovin, Stephen M; Barrow, Breanne M; Zraika, Sakeneh
- Abstract
Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high-fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed a HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut−/−) were generated by crossing Vil-Cre and floxed neprilysin mice. Neprilysin activity was almost abolished throughout the gut in NEPGut−/− mice, and was similar in plasma, pancreas, and kidney in NEPGut−/− vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut−/− displayed lower fasting plasma glucose levels, improved glucose tolerance, and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in HFD-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction.
- Subjects
NEPRILYSIN; GLUCOSE tolerance tests; BLOOD sugar; INSULIN; GLUCOSE intolerance; GASTRIC inhibitory polypeptide
- Publication
Endocrinology, 2024, Vol 165, Issue 8, p1
- ISSN
0013-7227
- Publication type
Article
- DOI
10.1210/endocr/bqae080