2013 Fiscal Year Final Research Report

The study of molecular mechanism of insulin receptor cleavage

Research Project

Project/Area Number	24790317
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Pathological medical chemistry
Research Institution	The University of Tokushima
Principal Investigator	YUASA Tomoyuki 徳島大学, 疾患酵素学研究センター, 准教授 (50304556)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	可溶性インスリン受容体 / インスリン抵抗性 / 糖尿病
Research Abstract	Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48 h) led to a significant increase in sIR levels in cells exposed to high glucose. Additionally, glucose-dependent increment of sIR was reversible in this model. Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. A calcium-dependent protease was shown to cleave IR extracellularly. These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage.

(3 results)