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NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion

Hussein Herz1, Yang Song1, Yuanchao Ye1

  • 1Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.

Nutrients
|January 11, 2022
PubMed
Abstract

Insights

Chronic non-steroidal anti-inflammatory drug (NSAID) use causes gut damage and weight loss in mice. This impairs glucose regulation and reduces glucagon-like peptide-1 (GLP-1) levels, impacting metabolic health.

Area of Science:

  • Gastroenterology
  • Endocrinology
  • Metabolic Research

Background:

  • Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used but can damage gut cells, including enteroendocrine cells.
  • NSAID-induced enteropathy is a known condition affecting the gastrointestinal tract.

Purpose of the Study:

  • To investigate the effects of chronic NSAID exposure on metabolic balance in a mouse model.
  • To determine if NSAIDs impact energy balance, glucose homeostasis, and GLP-1 levels.

Main Methods:

  • C57Blk/6J mice were administered NSAIDs via intragastric gavage.
  • Measurements included energy balance, glucose tolerance, and glucagon-like peptide-1 (GLP-1) levels.
  • Pharmacological interventions with a GLP-1 receptor antagonist (Exendin-9) and agonist (Exendin-4) were employed, alongside euglycemic-hyperinsulinemic clamps.

Main Results:

  • Chronic NSAID administration led to ileal ulcerations and weight loss in mice on a high-fat diet.
  • NSAID-treated mice showed impaired glucose tolerance and significantly attenuated glucose-stimulated GLP-1 levels.
  • GLP-1 receptor antagonism worsened glucose tolerance in controls but not NSAID-treated mice; Exendin-4 modulated insulin levels in ibuprofen-treated mice.

Conclusions:

  • Chronic NSAID use can cause small intestinal ulcerations, affecting GLP-1 production.
  • These changes impact hepatic insulin sensitivity and glucose production.
  • NSAID-induced enteropathy may contribute to metabolic dysregulation.
Keywords:
NSAID-induced enteropathyglucagon-like peptiode-1 (GLP-1)glucose tolerancehepatic glucose productionhepatic insulin sensitivitynon-steroidal anti-inflammatory drugs (NSAID)

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