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Hyaluronan induces ERK activation with minimal transcriptomic changes in pancreatic α-cells
Suguru Sonoyama1,2, Akiko Mizokami3, Tomomi Sano1
1Department of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Biochemistry and Biophysics Reports
|March 12, 2026
Summary
Hyaluronan (HA) accumulation in type 1 diabetes (T1D) islets activates alpha-cell signaling but causes minimal transcriptional changes. Additional inflammatory cues are likely needed to fully alter alpha-cells in T1D.
Area of Science:
- Endocrinology
- Immunology
- Cell Biology
Background:
- Type 1 diabetes (T1D) involves immune destruction of pancreatic beta-cells, sparing alpha-cells.
- Hyaluronan (HA), an extracellular matrix component, accumulates in T1D islets and promotes inflammation.
- Alpha-cells in T1D reside in a HA-rich microenvironment, prompting investigation into HA's role in their molecular alterations.
Purpose of the Study:
- To investigate if hyaluronan (HA) contributes to molecular changes in alpha-cells within the T1D microenvironment.
- To compare the effects of HA stimulation on alpha-cells with transcriptional profiles of alpha-cells from T1D donors.
Main Methods:
- A murine alpha-cell line (αTC1-6) was stimulated with low-molecular-weight HA.
- Intracellular signaling was assessed via extracellular signal-regulated kinase (ERK) phosphorylation.
- RNA sequencing was performed to analyze transcriptional changes, compared against public T1D alpha-cell datasets.
Main Results:
- HA stimulation induced sustained ERK phosphorylation, indicating intracellular signaling activation.
- Despite ERK activation, HA elicited minimal transcriptional changes compared to T1D alpha-cells.
- Gene set enrichment analysis showed a shared modest reduction in peroxisome proliferator-activated receptor (PPAR) signaling in both HA-stimulated and T1D alpha-cells.
Conclusions:
- Hyaluronan (HA) alone does not fully explain the extensive transcriptional remodeling observed in T1D alpha-cells.
- Additional inflammatory or microenvironmental factors are likely required to induce the full spectrum of T1D-associated alpha-cell alterations.
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