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Open AccessArticle

Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

1
Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
2
Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK
3
Department of Pharmacy, Faculty of Medicine, Univesitas Brawijaya, Malang 65145, Indonesia
4
Department of Anatomical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
5
Institute of Tropical Disease, Universitas Airlangga, Surabaya 60286, Indonesia
6
Department of Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Luigi Milella
Molecules 2020, 25(19), 4381; https://doi.org/10.3390/molecules25194381
Received: 28 August 2020 / Revised: 18 September 2020 / Accepted: 22 September 2020 / Published: 24 September 2020
Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM—type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic β cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic β cells. It induces β cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic β cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic β cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus. View Full-Text
Keywords: diabetes mellitus; MST1/2; Hippo pathway; XMU-MP-1 diabetes mellitus; MST1/2; Hippo pathway; XMU-MP-1
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Faizah, Z.; Amanda, B.; Ashari, F.Y.; Triastuti, E.; Oxtoby, R.; Rahaju, A.S.; Aziz, M.A.; Lusida, M.I.; Oceandy, D. Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice. Molecules 2020, 25, 4381.

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