Scinderin-driven Golgi Actin Remodeling coordinates GLP-1 and insulin secretion to regulate glucose homeostasis

Martin Diaz, L.; Patrikainen, M.; Chongtham, C.; Gupta, A.; Dotsenko, V.; Ojanen, M. J. T.; Arrojo Martins, F. T.; George, J. J.; Davidsson, R.; Hakanen, S.; Eerola, K.; Savontaus, E.; Saarimaki-Vire, J.; Balboa, D.; Isola, J.; Laiho, J. E.; Hyoty, H.; Otonkoski, T.; Vihinen-Ranta, M.; Toivola, D. M.; Viiri, K.

doi:10.64898/2026.05.28.728433

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bioRxiv · 10.64898/2026.05.28.728433

Scinderin-driven Golgi Actin Remodeling coordinates GLP-1 and insulin secretion to regulate glucose homeostasis

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Abstract

Maintenance of glucose homeostasis requires coordinated hormone secretion from intestinal enteroendocrine cells and pancreatic {beta}-cells, yet the intracellular mechanisms that couple nutrient sensing to endocrine output remain poorly defined. Here, we identify the actin remodeler Scinderin (SCIN) as a shared regulator of hormone secretion across these systems. SCIN is selectively expressed in enteroendocrine L-cells and pancreatic {beta}-cells, where it localizes to phosphatidylinositol-4-phosphate (PI(4)P)-enriched Golgi membranes and controls Golgi-associated actin dynamics. Loss of SCIN disrupts Golgi organization, impairs prohormone trafficking, and reduces secretory granule formation, resulting in defective nutrient-stimulated GLP-1 and insulin secretion while preserving cAMP-dependent amplification pathways. In vivo, tissue-specific deletion of Scin compromises incretin responses, {beta}-cell insulin secretion, and systemic glucose homeostasis. Consistent with these findings, SCIN expression is reduced in human diabetic {beta}-cells and associates with stress-related loss of {beta}-cell maturity. Transcriptomic analyses reveal a conserved Golgi stress program upon SCIN loss, linking intracellular trafficking defects to endocrine dysfunction. Together, our results identify SCIN-dependent Golgi actin remodeling as a rate-limiting intracellular mechanism coordinating enteroendocrine and pancreatic hormone secretion. This work uncovers a shared, targetable node controlling endocrine output, providing a mechanistic link between secretory pathway dysfunction and diabetes.

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Martin Diaz, L., Patrikainen, M., Chongtham, C., Gupta, A., Dotsenko, V., Ojanen, M. J. T., Arrojo Martins, F. T., George, J. J., Davidsson, R., Hakanen, S., Eerola, K., Savontaus, E., Saarimaki-Vire, J., Balboa, D., Isola, J., Laiho, J. E., Hyoty, H., Otonkoski, T., Vihinen-Ranta, M., Toivola, D. M., Viiri, K.. 2026-05-28. Scinderin-driven Golgi Actin Remodeling coordinates GLP-1 and insulin secretion to regulate glucose homeostasis. https://doi.org/10.64898/2026.05.28.728433

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