Culprit in reducing effectiveness of insulin identified

Culprit in reducing effectiveness of insulin identified
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. This attenuates 4) insulin-mediated Akt phosphorylation and 5) glucose uptake. Credit: Osaka University

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 . Insulin binds to cellular 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 , played a role in developing obesity. However, it was not known that adipocytokine activated on adipocytes themselves to control . 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., 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.

More information: Jihoon Shin et al, SDF-1 is an Autocrine Insulin-Desensitizing Factor in Adipocytes, Diabetes (2018). DOI: 10.2337/db17-0706

Journal information: Diabetes

Provided by Osaka University
Citation: Culprit in reducing effectiveness of insulin identified (2018, April 26) retrieved 3 October 2023 from
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