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Updated: May 21, 2026
Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells
Published on: June 15, 2013
Gene networks modified by sulphonylureas in beta cells: a pathway-based analysis of insulin secretion and cell death
Nils E Magnusson1, Lars Dyrskjøt, Daniela Grimm
1Institute of Biomedicine, Pharmacology, University of Aarhus, Aarhus, Denmark. nm@farm.au.dk
Abstract:
Sulphonylureas (SUs) used in the treatment for type 2 diabetes have been shown to result in different clinical outcome. This study hypothesized that three widely used SUs, glibenclamide, glimepiride and gliclazide, may affect function and survival of insulin-producing cells differently. To evaluate differences between SUs, insulin secretion and cell death were measured, and genome-wide gene expression patterns were compared using a bioinformatics approach focusing on functional relationships between molecules. Insulin-producing INS-1E cells exposed to SUs for 6 and 24 hr were assayed using GeneChip. Cluster and pathway analyses were used to identify differentially expressed genes and patterns of potential biological functions associated with SU treatment. Cell death was measured using acridine orange/Hoechst 33342 staining. Short-term treatment (6 hr) yielded up-regulation of insulin secretion and genes associated with insulin secretion for all three SUs applied. While long-term treatment (24-72 hr) with gliclazide did not change gene expression or cell survival, treatment with glibenclamide or glimepiride up-regulated genes associated with oxidative stress and hypoxia, but did not induce cell death. Short-term treatment with SUs initiates gene regulation that can be attributed to insulin secretion with few differences between individual SUs. This regulation was temporal and returned to baseline after 24 hr. Individual differences observed after 24-72 hr indicate that glibenclamide and glimepiride induce potentially harmful cell signalling insufficient for triggering beta cell death.
Insights
Different sulfonylureas (SUs) impact type 2 diabetes treatment outcomes. Glibenclamide and glimepiride, unlike gliclazide, may induce harmful cell signaling in insulin-producing cells over time.
Area of Science:
- Endocrinology
- Pharmacology
- Molecular Biology
Background:
- Sulfonylureas (SUs) are common type 2 diabetes treatments.
- Clinical outcomes vary significantly among different SUs.
- Potential differential effects on pancreatic beta-cell function and survival are not fully understood.
Purpose of the Study:
- To investigate the distinct effects of three widely used SUs (glibenclamide, glimepiride, gliclazide) on insulin-producing cell function and survival.
- To compare genome-wide gene expression patterns induced by these SUs.
- To identify molecular mechanisms underlying differential SU effects.
Main Methods:
- Insulin-secreting INS-1E cells were treated with glibenclamide, glimepiride, and gliclazide for 6 and 24 hours.
- Genome-wide gene expression was analyzed using GeneChip and bioinformatics approaches (cluster and pathway analysis).
- Cell death was quantified using acridine orange/Hoechst 33342 staining.
Main Results:
- Short-term (6 hr) SU treatment upregulated insulin secretion and related genes similarly across all agents.
- Long-term (24-72 hr) treatment with gliclazide showed no significant changes in gene expression or cell survival.
- Glibenclamide and glimepiride induced genes linked to oxidative stress and hypoxia but did not cause cell death after 24-72 hours.
Conclusions:
- Short-term SU exposure triggers temporal, similar gene regulation related to insulin secretion.
- Long-term exposure reveals distinct effects: glibenclamide and glimepiride induce potentially detrimental signaling pathways in beta cells.
- These findings suggest glibenclamide and glimepiride may have different long-term implications for beta-cell health compared to gliclazide.
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