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High fructose rewires gut glucose sensing via glucagon-like peptide 2 to impair metabolic regulation in mice.
Mol Metab
January 2025
Québec Heart and Lung Institute Research Center, Université Laval - 2725, Ch. Sainte-Foy, Québec, QC, Canada, G1V 4G5; Department of Medicine, Faculty of Medicine, Université Laval - 1050 Av. de la Médecine, Québec, QC, Canada, G1V 0A6; Institute of Nutrition and Functional Foods, Université Laval - 2440 Bd. Hochelaga, Québec, QC, Canada, G1V 0A6. Electronic address:
Background: Increased fructose consumption contributes to type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms are ill-defined. Gut nutrient sensing involves enterohormones like Glucagon-like peptide (Glp)2, which regulates the absorptive capacity of luminal nutrients. While glucose is the primary dietary energy source absorbed in the gut, it is unknown whether excess fructose alters gut glucose sensing to impair blood glucose regulation and liver homeostasis.
View Article and Find Full Text PDFCreating Glepaglutide, the First Long-Acting GLP-2 Analogue to Enable a Ready-to-Use Injection.
J Med Chem
January 2025
Zealand Pharma A/S, Sydmarken 11, 2860 Søborg, Denmark.
Human glucagon-like peptide-2 (hGLP-2) receptor agonists have a benefit for the treatment of short bowel syndrome (SBS) and potentially other intestinal diseases (e.g., IBD).
View Article and Find Full Text PDF.
Biochem Pharmacol
January 2025
College of Medicine, Jiaxing University, Jiaxing 314001, PR China; Taizhou Hospital, Zhejiang University, Taizhou 317000, PR China. Electronic address:
Glucagon-like peptide 2 (GLP-2) is a proglucagon-derived peptide released by intestinal endocrine cells. However, its therapeutic potential is limited by rapid inactivation via dipeptidyl peptidase-IV. The elucidation of three-dimensional structures of G-protein-coupled receptors, including GLP-2 receptor, has facilitated the rational design of novel peptide therapeutics.
View Article and Find Full Text PDFPlasma glucagon-like peptide-2 in cats with chronic enteropathies.
J Feline Med Surg
January 2025
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Objectives: The objective of this study was to compare plasma glucagon-like peptide-2 (GLP-2) concentrations in cats with chronic enteropathies (CE) with those of healthy cats.
Methods: Nineteen client-owned cats with a histopathologic diagnosis of either idiopathic chronic enteropathy (CIE) or low-grade lymphoma and six healthy client-owned cats were enrolled in a prospective study between 2 December 2021 and 9 June 2023. Fasted and postprandial plasma GLP-2 concentrations were measured via ELISA in CE cats at the time gastrointestinal biopsies were obtained and before CE treatment.
Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.
Int J Mol Sci
January 2025
Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.
Type 2 diabetes (T2D), the most common form, is marked by insulin resistance and β-cell failure. β-cell dysfunction under high-glucose-high-lipid (HG-HL) conditions is a key contributor to the progression of T2D. This study evaluates the comparative effects of 10 nM semaglutide, 10 nM tirzepatide, and 1 mM metformin, both alone and in combination, on INS-1 β-cell maintenance and function under HG-HL conditions.
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