1) Fasting or obesity induces SDF-1 expression in adipocytes. 2) Its autocrine action activates ERK signaling. 3) SDF-1-induced ERK signal concomitantly induces serine phosphorylation of IRS-1 protein and degrades IRS-1 protein.
Scientists at Osaka University have discovered that Stromal-derived factor-1 (SDF-1) secreted from adipocytes reduces the effectiveness of insulin in adipocytes and decreased insulin-induced glucose uptake.
Insulin is a hormone that facilitates glucose uptake. Insulin binds to cellular insulin receptors to activate Insulin Receptor Substrate 1 (IRS-1), taking in sugar through phosphorylation of Akt. If insulin loses its effectiveness, cells in the body become unable to take up glucose, and blood sugar levels rise, leading to diabetes.
A group of researchers led by Atsunori Fukuhara has reported that adipocytokine, or cell signaling proteins secreted by the adipose tissue, played a role in developing obesity. However, it was not known that adipocytokine activated on adipocytes themselves to control insulin sensitivity. SDF-1, one of the adipocytokines, is the most predominantly expressed chemokine; however, its action on glucose uptake in cells had not been analyzed.
Using microarray database analysis, the scientists identified SDF-1 as a factor to enhance expression in adipocytes in both fasting and obese states and found that SDF-1 reduced the effectiveness of insulin in adipocytes. In actuality, in SDF-1 knockout mice, insulin-induced glucose uptake increased (i.e., blood sugar levels decreased), and insulin efficacy improved (i.e., insulin sensitivity was enhanced). Their research results were published in Diabetes.
Based on the results of this study, it is expected that insulin sensitivity in adipocytes will increase by inactivating the SDF-1 signaling pathway, which will lead to treatment of obese type 2 diabetes.