Dual Effect of 4-Methylumbelliferone on INS1E Cells: Enhancing Migration and Glucose-Stimulated Insulin Secretion

TL;DR

4-Methylumbelliferone improves insulin secretion and cell migration in insulinoma cells, possibly aiding diabetes treatment and islet transplantation.

Contribution

First study to show 4MU enhances insulin secretion and alters cell morphology in INS1E cells.

Findings

4MU treatment improves glucose-stimulated insulin secretion in INS1E cells.

4MU induces morphological changes and affects cell adhesion properties.

Insulin secretion is not linked to hyaluronan production in these cells.

Abstract

Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU may also affect cellular metabolism. In this study, we utilize the rat insulinoma beta cell line (INS-1E) cultured in both two-dimensional (2D) and three-dimensional (3D) experimental settings (pseudo islets), as an in vitro model to study beta cell functionality. For the first time, we observed that treating INS1E cells with 4MU results in improved insulin secretion. Additionally, we discovered that 4MU treatment elicited morphological changes from multilayer to monolayer conditions, along with a varied distribution of insulin granules and cell adhesion properties. Notably, we found that insulin secretion is not correlated with HA production. The same result was observed in co-culture experiments involving INS-1E cells and stromal vascular fraction (SVF) from adipose tissue. These experiments aim to investigate the effects of 4MU on beta cells in the context of its potential use in early-stage type 1 diabetes and in enhancing islet transplantation outcomes.

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