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Publication Detail
Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    McLean BA, Wong CK, Campbell JE, Hodson DJ, Trapp S, Drucker DJ
  • Publisher:
    Endocrine Society
  • Publication date:
  • Journal:
    Endocrine Reviews
  • Status:
  • Country:
    United States
  • Print ISSN:
  • PII:
  • Language:
  • Keywords:
    Diabetes, brain, cardiovascular, gastrointestinal tract, islets, obesity, receptor
Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. Classic notions of GLP-1 acting as a meal-stimulated hormone from the distal gut are challenged by data supporting production of GLP-1 in the endocrine pancreas, and by the importance of brain-derived GLP-1 in the control of neural activity. Moreover, attribution of direct vs. indirect actions of GLP-1 is difficult, as many tissue and cellular targets of GLP-1 action do not exhibit robust or detectable GLP-1R expression. Furthermore, reliable detection of the GLP-1R is technically challenging, highly method-dependent, and subject to misinterpretation. Here we revisit the actions of GLP-1, scrutinizing key concepts supporting gut vs. extra-intestinal GLP-1 synthesis and secretion. We discuss new insights refining cellular localization of GLP-1R expression and integrate recent data to refine our understanding of how and where GLP-1 acts to control inflammation, cardiovascular function, islet hormone secretion, gastric emptying, appetite, and body weight. These findings update our knowledge of cell types and mechanisms linking endogenous vs. pharmacological GLP-1 action to activation of the canonical GLP-1R, and the control of metabolic activity in multiple organs.
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