Insulin, Growth Hormone Receptor Structure And Function Of Research

Insulin is a multi-function protein, possessing both metabolic and mitogenic ability. Insulin stimulates glucose uptake by inducing the translocation of GLUT4 to plasma membrane from intracellular pools, which is the rate-limiting step of glucose metabolism. In the meanwhile, glycogen synthesis and lipogenesis are also activated. However, insulin has the property of self-association at high concentration, which affects the clinic application of insulin. These years, research on rapid-acting monomer insulin has been the focus of the clinic application of insulin. Based on our previous research and others' reports, Professor Feng You-Min's lab and our lab obtained a series of insulin mutants, of which some can not self-associate at high concentration. In this part, we mainly studied the physiological functions of [B9GluB10Asp]-human insulin, a monoinsulin, in isolated fat cells. Our data showed that the abilities of [B9GluB10Asp]-human insulin to stimulte glucose uptake and lipogenesis are 45 % and 40 % of that of porcine insulin, respectively. [B9GluB10Asp]-human insulin bound to its receptor with ability of 31 % relative to porcine insulin and stimulated increases in the GLUT4 tanslocation to plasma membrane from intracellular pools and the phosphorylation of insulin receptor β-subunit, being 58 % and 46 % compared to porcine insulin, respectively. Compared with the high bioactivity in vitro of [B10Asp]-human insulin, it is clearly shown that B9Ser is vital to the activity of insulin.