Issue 14, 2025

A glucose-responsive alginate-based hydrogel laden with modified GLP-1 and telmisartan ameliorates type 2 diabetes and reduces liver and kidney toxicities

Abstract

The pathophysiology associated with type 2 diabetes mellitus (T2DM) includes insulin resistance, increased oxidative stress, a pro-inflammatory macrophage population, and dysfunction of pancreatic β cells in the islets of Langerhans, along with hepato- and nephro-toxicity. In this study, an injectable glucose-responsive hydrogel (Diabogel) was developed using alginate and 3-aminophenyl boronic acid to deliver modified glucagon-like peptide-1, insulinoma cell-derived extracellular vesicles, and telmisartan. Diabogel demonstrated cytocompatibility, decreased reactive oxygen species, enhanced insulin synthesis, and improved glucose uptake in vitro. In a high-fat diet/streptozotocin-induced murine model of T2DM, Diabogel lowered blood glucose levels, maintained body weight, and increased insulin expression. Furthermore, it promoted an anti-inflammatory microenvironment in the pancreas by regulating macrophage phenotype and the expression of NF-κB, supported cellular proliferation, and restored the pancreatic islets. In addition, Diabogel treatment significantly lowered the serum levels of pro-inflammatory cytokines and enhanced anti-inflammatory cytokines. Interestingly, Diabogel treatment also lowered diabetes-associated hepato- and nephro-toxicity. Taken together, Diabogel may serve as a potential approach for the treatment of T2DM, regulating blood glucose levels, restoring pancreatic β cell function, and reducing hepatic and renal toxicities.

Graphical abstract: A glucose-responsive alginate-based hydrogel laden with modified GLP-1 and telmisartan ameliorates type 2 diabetes and reduces liver and kidney toxicities

Supplementary files

Article information

Article type
Paper
Submitted
08 Oct 2024
Accepted
25 Feb 2025
First published
17 Mar 2025

J. Mater. Chem. B, 2025,13, 4419-4432

A glucose-responsive alginate-based hydrogel laden with modified GLP-1 and telmisartan ameliorates type 2 diabetes and reduces liver and kidney toxicities

A. Singh, Khushboo, M. Pandey, S. Mattoo, S. K. Pore and J. Bhattacharyya, J. Mater. Chem. B, 2025, 13, 4419 DOI: 10.1039/D4TB02261K

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