
Cellular Sites and Mechanisms Linking Reduction of Dipeptidyl Peptidase-4 Activity to Control of Incretin Hormone Action and Glucose Homeostasis.
Pharmacological inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme potentiates incretin action and is widely used to treat type 2 diabetes. Nevertheless, the precise cells and tissues critical for incretin degradation and glucose homeostasis remain unknown. Here, we use mouse genetics and pharmacologic DPP4 inhibition to identify DPP4+ cell types essential for incretin action. Although enterocyte DPP4 accounted for substantial intestinal DPP4 activity, ablation of enterocyte DPP4 in Dpp4Gut-/- mice did not produce alterations in plasma DPP4 activity, incretin hormone levels, and glucose tolerance. In contrast, endothelial cell (EC)-derived DPP4 contributed substantially to levels of soluble plasma DPP4 activity, incretin degradation, and glucose control. Surprisingly, DPP4+ cells of bone marrow origin mediated the selective degradation of fasting GIP, but not GLP-1. Collectively, these findings identify distinct roles for DPP4 in the EC versus the bone marrow compartment for selective incretin degradation and DPP4i-mediated glucoregulation.
Duke Scholars
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Related Subject Headings
- Sitagliptin Phosphate
- Models, Biological
- Mice
- Male
- Intestines
- Intestinal Mucosa
- Insulin Resistance
- Incretins
- Homeostasis
- Glucose Tolerance Test
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sitagliptin Phosphate
- Models, Biological
- Mice
- Male
- Intestines
- Intestinal Mucosa
- Insulin Resistance
- Incretins
- Homeostasis
- Glucose Tolerance Test