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Keratin 8 modulates β-cell stress responses and normoglycaemia

Alam, Catharina M.; Silvander, Jonas S.G.; Daniel, Ebot N.; Tao, Guo-Zhong; Kvarnstr�m, Sofie M.; Alam, Parvez; Omary, M. Bishr; H�nninen, Arno; Toivola, Diana M.


Jonas S.G. Silvander

Ebot N. Daniel

Guo-Zhong Tao

Sofie M. Kvarnstr�m

Parvez Alam

M. Bishr Omary

Arno H�nninen

Diana M. Toivola


Keratin intermediate filament (IF) proteins are epithelial cell cytoskeletal components that provide structural stability and protection from cell stress, among other cellular and tissue-specific functions. Numerous human diseases are associated with IF gene mutations, but the function of keratins in the endocrine pancreas and their potential significance for glycaemic control are unknown. The impact of keratins on β-cell organisation and systemic glucose control was assessed using keratin 8 (K8) wild-type (K8(+/+)) and K8 knockout (K8(-/-)) mice. Islet β-cell keratins were characterised under basal conditions, in streptozotocin (STZ)-induced diabetes and in non-obese diabetic (NOD) mice. STZ-induced diabetes incidence and islet damage was assessed in K8(+/+) and K8(-/-) mice. K8 and K18 were the predominant keratins in islet β-cells and K8(-/-) mice expressed only remnant K18 and K7. K8 deletion resulted in lower fasting glucose levels, increased glucose tolerance and insulin sensitivity, reduced glucose-stimulated insulin secretion and decreased pancreatic insulin content. GLUT2 localisation and insulin vesicle morphology were disrupted in K8(-/-) β-cells. The increased levels of cytoplasmic GLUT2 correlated with resistance to high-dose STZ-induced injury in K8(-/-) mice. However, K8 deletion conferred no long-term protection from STZ-induced diabetes and prolonged STZ-induced stress caused increased exocrine damage in K8(-/-) mice. β-cell keratin upregulation occurred 2 weeks after treatments with low-dose STZ in K8(+/+) mice and in diabetic NOD mice, suggesting a role for keratins, particularly in non-acute islet stress responses. These results demonstrate previously unrecognised functions for keratins in β-cell intracellular organisation, as well as for systemic blood glucose control under basal conditions and in diabetes-induced stress.


Alam, C. M., Silvander, J. S., Daniel, E. N., Tao, G., Kvarnström, S. M., Alam, P., …Toivola, D. M. (2013). Keratin 8 modulates β-cell stress responses and normoglycaemia. Journal of Cell Science, 126(24), 5635-5644.

Journal Article Type Article
Acceptance Date Sep 30, 2013
Publication Date 2013-12
Deposit Date May 26, 2022
Journal Journal of cell science
Print ISSN 0021-9533
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 126
Issue 24
Pages 5635-5644
Keywords Keratin, K8, Blood glucose, Diabetes model, Endocrine pancreas
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