Home
Resources
Publications
Decreased Levels of Keratin 8 Sensitize Mice to Streptozotocin-Induced Diabetes

Decreased Levels of Keratin 8 Sensitize Mice to Streptozotocin-Induced Diabetes

C M Alam, J S G Silvander, T O Helenius, D M Toivola

Acta Physiol (Oxf). 2018 Oct;224(2):e13085.

PMID: 29719117

Abstract:

Aim:
Diabetes is a result of an interplay between genetic, environmental and lifestyle factors. Keratin intermediate filaments are stress proteins in epithelial cells, and keratin mutations predispose to several human diseases. However, the involvement of keratins in diabetes is not well known. K8 and its partner K18 are the main β-cell keratins, and knockout of K8 (K8-/- ) in mice causes mislocalization of glucose transporter 2, mitochondrial defects, reduced insulin content and altered systemic glucose/insulin control. We hypothesize that K8/K18 offer protection during β-cell stress and that decreased K8 levels contribute to diabetes susceptibility.
Methods:
K8-heterozygous knockout (K8+/- ) and wild-type (K8+/+ ) mice were used to evaluate the influence of keratin levels on endocrine pancreatic function and diabetes development under basal conditions and after T1D streptozotocin (STZ)-induced β-cell stress and T2D high-fat diet (HFD).
Results:
Murine K8+/- endocrine islets express ~50% less K8/K18 compared with K8+/+ . The decreased keratin levels have little impact on basal systemic glucose/insulin regulation, β-cell health or insulin levels. Diabetes incidence and blood glucose levels are significantly higher in K8+/- mice after low-dose/chronic STZ treatment, and STZ causes more β-cell damage and polyuria in K8+/- compared with K8+/+ . K8 appears upregulated 5 weeks after STZ treatment in K8+/+ islets but not in K8+/- . K8+/- mice showed no major susceptibility risk to HFD compared to K8+/+ .
Conclusion:
Partial K8 deficiency reduces β-cell stress tolerance and aggravates diabetes development in response to STZ, while there is no major susceptibility to HFD.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241175	Keratin-8 human			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: