SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors

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Lehtonen , S 2020 , ' SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors ' , Acta Physiologica , vol. 228 , no. 1 , 13349 . https://doi.org/10.1111/apha.13349

Title: SHIPping out diabetes-Metformin, an old friend among new SHIP2 inhibitors
Author: Lehtonen, Sanna
Contributor organization: Department of Pathology
University Management
Sanna Lehtonen research group
University of Helsinki
Faculty of Medicine
CAMM - Research Program for Clinical and Molecular Metabolism
Research Programs Unit
Date: 2020-01
Language: eng
Number of pages: 22
Belongs to series: Acta Physiologica
ISSN: 1748-1708
DOI: https://doi.org/10.1111/apha.13349
URI: http://hdl.handle.net/10138/312610
Abstract: SHIP2 (Src homology 2 domain-containing inositol 5 '-phosphatase 2) belongs to the family of 5 '-phosphatases. It regulates the phosphoinositide 3-kinase (PI3K)-mediated insulin signalling cascade by dephosphorylating the 5 '-position of PtdIns(3,4,5)P3 to generate PtdIns(3,4)P2, suppressing the activity of the pathway. SHIP2 mouse models and genetic studies in human propose that increased expression or activity of SHIP2 contributes to the pathogenesis of the metabolic syndrome, hypertension and type 2 diabetes. This has raised great interest to identify SHIP2 inhibitors that could be used to design new treatments for metabolic diseases. This review summarizes the central mechanisms associated with the development of diabetic kidney disease, including the role of insulin resistance, and then moves on to describe the function of SHIP2 as a regulator of metabolism in mouse models. Finally, the identification of SHIP2 inhibitors and their effects on metabolic processes in vitro and in vivo are outlined. One of the newly identified SHIP2 inhibitors is metformin, the first-line medication prescribed to patients with type 2 diabetes, further boosting the attraction of SHIP2 as a treatment target to ameliorate metabolic disorders.
Subject: diabetes
diabetic kidney disease
insulin resistance
insulin signalling
lipid phosphatase
podocyte
LIPID PHOSPHATASE SHIP2
ACTIVATED PROTEIN-KINASE
INOSITOL 5-PHOSPHATASE SHIP2
ENDOTHELIAL GROWTH-FACTOR
5'-PHOSPHATASE-2 GENE POLYMORPHISMS
ENDOPLASMIC-RETICULUM STRESS
URINARY ALBUMIN EXCRETION
INSULIN-RESISTANCE
GLUCOSE-METABOLISM
HUMAN PODOCYTES
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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