NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion
| Autor: | Hussein Herz, Yang Song, Yuanchao Ye, Liping Tian, Benjamin Linden, Marwa Abu El Haija, Yi Chu, Justin L. Grobe, Randall W. Lengeling, Mohamad Mokadem |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
glucose tolerance
Ibuprofen Diet High-Fat Article Glucagon-Like Peptide-1 Receptor non-steroidal anti-inflammatory drugs (NSAID) glucagon-like peptiode-1 (GLP-1) NSAID-induced enteropathy hepatic glucose production hepatic insulin sensitivity Mice Glucagon-Like Peptide 1 Glucose Intolerance Animals Insulin TX341-641 Nutrition and Dietetics Nutrition. Foods and food supply Anti-Inflammatory Agents Non-Steroidal digestive oral and skin physiology Mice Inbred C57BL Disease Models Animal Intestinal Diseases Glucose Liver Glucose Clamp Technique Insulin Resistance Food Science |
| Zdroj: | Nutrients, Vol 14, Iss 120, p 120 (2022) Nutrients Nutrients; Volume 14; Issue 1; Pages: 120 |
| ISSN: | 2072-6643 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|