Affiliation:
1. Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR) Gunma University Maebashi Japan
2. Department of Endocrinology and Metabolism, Graduate School of Medicine Yokohama City University Yokohama City Japan
Abstract
AbstractThe decline in β‐cell mass due to the failure of β‐cell compensation is one cause of the development of type 2 diabetes. Therefore, elucidation of the mechanism by which an adaptive increase in β‐cell mass occurs in vivo will lead to the development of a cure for diabetes. Insulin and insulin receptor (IR)‐mediated signaling pathways play an important role in the mechanism that increases β‐cell mass by compensatory β‐cell proliferation in response to chronic insulin resistance. However, whether IR is required for compensatory β‐cell proliferation remains controversial in some situations. It might be possible that IR acts as a scaffold for the signaling complex independent of its ligand. It has also been reported that the forkhead box protein M1/polo‐like kinase 1/centromere protein A pathway plays a central role in adaptive β‐cell proliferation during diet‐induced obesity, hyperglycemia, pregnancy, aging and acute insulin resistance. We recently reported that the cross‐talk of islets with fat tissue, in addition to the liver, through humoral factors is involved in adaptive β‐cell proliferation. This accommodative response of β‐cell proliferation through adipocytes was observed particularly under an acute insulin resistance state in an IR/insulin signal‐independent and forkhead box protein M1/polo‐like kinase 1/centromere protein A pathway‐dependent manner. A remaining barrier for the treatment of human diabetes using β‐cells is the differences between human and rodent islets. In this review, the focus is on signaling pathways that regulate adaptive β‐cell proliferation for the treatment of diabetes considering the abovementioned issues.
Funder
Japan Agency for Medical Research and Development
Astellas Foundation for Research on Metabolic Disorders
Daiichi Sankyo Foundation of Life Science
Japan Diabetes Foundation
Japan Diabetes Society
Japan IDDM network
Manpei Suzuki Diabetes Foundation
Ministry of Education, Culture, Sports, Science and Technology
Mochida Memorial Foundation for Medical and Pharmaceutical Research
Naito Foundation
Uehara Memorial Foundation
Taiju Life Social Welfare Foundation
Subject
General Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
1 articles.
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