Journal article
NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion
Nutrients, Vol.14(1), p.120
01/01/2022
DOI: 10.3390/nu14010120
PMCID: PMC8746549
PMID: 35010994
Abstract
Background/Aim: Given their widespread use and their notorious effects on the lining of gut cells, including the enteroendocrine cells, we explored if chronic exposure to non-steroidal anti-inflammatory drugs (NSAIDs) affects metabolic balance in a mouse model of NSAID-induced enteropathy. Method: We administered variable NSAIDs to C57Blk/6J mice through intragastric gavage and measured their energy balance, glucose hemostasis, and GLP-1 levels. We treated them with Exendin-9 and Exendin-4 and ran a euglycemic-hyperinsulinemic clamp. Results: Chronic administration of multiple NSAIDs to C57Blk/6J mice induces ileal ulcerations and weight loss in animals consuming a high-fat diet. Despite losing weight, NSAID-treated mice exhibit no improvement in their glucose tolerance. Furthermore, glucose-stimulated (glucagon-like peptide -1) GLP-1 is significantly attenuated in the NSAID-treated groups. In addition, Exendin-9-a GLP-1 receptor antagonist-worsens glucose tolerance in the control group but not in the NSAID-treated group. Finally, the hyper-insulinemic euglycemic clamp study shows that endogenous glucose production, total glucose disposal, and their associated insulin levels were similar among an ibuprofen-treated group and its control. Exendin-4, a GLP-1 receptor agonist, reduces insulin levels in the ibuprofen group compared to their controls for the same glucose exchange rates. Conclusions: Chronic NSAID use can induce small intestinal ulcerations, which can affect intestinal GLP-1 production, hepatic insulin sensitivity, and consequently, hepatic glucose production.
Details
- Title: Subtitle
- NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion
- Creators
- Hussein Herz - Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAYang Song - Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAYuanchao Ye - University of IowaLiping Tian - University of IowaBenjamin Linden - Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAMarwa Abu El Haija - Univ Iowa, Stead Family Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USAYi Chu - Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USAJustin L. Grobe - Medical College of WisconsinRandall W. LengelingMohamad Mokadem - Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Nutrients, Vol.14(1), p.120
- DOI
- 10.3390/nu14010120
- PMID
- 35010994
- PMCID
- PMC8746549
- NLM abbreviation
- Nutrients
- ISSN
- 2072-6643
- eISSN
- 2072-6643
- Publisher
- Mdpi
- Number of pages
- 13
- Grant note
- DOI: 10.13039/100000738, name: United States Department of Veterans Affairs, award: I01 BX004774
- Language
- English
- Date published
- 01/01/2022
- Academic Unit
- Gastroenterology and Hepatology; Surgery; Internal Medicine
- Record Identifier
- 9984360044502771
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