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Related Concept Videos

Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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Injectable thermosensitive hydrogel to modulate tolerogenic dendritic cells under hyperglycemic condition.

Yi Zhu1, Daniel Winer2,3,4,5, Cynthia Goh6,7

  • 1Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON, M5G 1G6, Canada. Annie.Shrestha@dentistry.utoronto.ca.

Biomaterials Science
|February 1, 2023
PubMed
Summary
This summary is machine-generated.

A novel hydrogel therapy effectively modulated dendritic cells (DCs) in diabetic periodontitis models. This treatment promoted regulatory T-cells, reducing inflammation and enhancing healing potential for diabetic periodontitis.

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Periodontology

Background:

  • Diabetes mellitus-induced hyperglycemia exacerbates periodontitis by promoting inflammation.
  • Dendritic cells (DCs) are key immune regulators implicated in periodontitis pathogenesis.
  • Targeting DCs offers a therapeutic strategy for diabetic periodontitis.

Purpose of the Study:

  • To develop and characterize a chitosan-based thermosensitive injectable hydrogel (TISH) for modulating DCs.
  • To investigate the efficacy of TISH loaded with GM-CSF and resveratrol (TISH(G + R)) in a diabetic periodontitis context.
  • To assess TISH(G + R)'s ability to induce tolerogenic DCs and regulatory T-cells.

Main Methods:

  • Development of a chitosan-based thermosensitive injectable hydrogel (TISH).
  • Loading of granulocyte-macrophage colony-stimulating factor (GM-CSF) and resveratrol into TISH.
  • In vitro assessment of DC maturation and gene expression under hyperglycemic conditions.
  • In vitro co-culture of modified DCs with T-cells to evaluate regulatory T-cell induction.
  • In vivo subcutaneous injection in mice to assess DC and regulatory T-cell infiltration.

Main Results:

  • TISH(G + R) demonstrated good biocompatibility and cell penetration.
  • In vitro, TISH(G + R) reduced DC maturation markers (CD80, CD83, CD86) and upregulated tolerogenic genes (FOXP3, SOCS3, TGFß, IL10) under hyperglycemia.
  • Tolerogenic DCs induced regulatory T-cell differentiation in vitro, confirmed by elevated FOXP3, TGFβ, and IL-10.
  • In vivo studies showed significant infiltration of DCs and regulatory T-cells following TISH(G + R) injection.

Conclusions:

  • TISH was successfully developed as an injectable hydrogel for modulating DCs towards a tolerogenic phenotype.
  • TISH(G + R) effectively induces regulatory T-cells under hyperglycemic conditions, attenuating inflammation.
  • This TISH-based approach shows significant potential for improving periodontal health in diabetic periodontitis.