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Has the Link between Obesity and Insulin Resistance Been Discovered?

Midkine, also known as MK, a protein cytokine that promotes cell proliferation, differentiation, survival, and migration, may hold the clues…. 

Obesity is a medical condition widely associated with the development of complications including type 2 diabetes, insulin resistance, and cardiovascular diseases. Obesity leads to an increased production of proinflammatory cytokines (proteins that aid in cell-to-cell communication), which induce chronic inflammation and insulin resistance.

Midkine, also known as MK, is a protein cytokine that promotes cell proliferation, differentiation, survival, and migration. It is synthesized and secreted by adipocytes. Previous studies have shown that obese and diabetic children have significantly higher levels of serum midkine than the control subjects. This current study investigates the association between midkine and obesity, as well as the impact of midkine on insulin signaling adipocytes.

The study looked at 135 individuals and divided the subjects into two groups: normal weight, and obese subjects. Cells were cultured from the subjects, with RNA being extracted from adipose tissues and amplified via PCR analysis and whole cell protein extraction was obtained via a western blot analysis. Mouse subjects were also used and the midkine levels in their adipose tissue was analyzed. The final analysis of the midkine protein in both mice and humans was as follows:

  • Midkine expression is upregulated by inflammatory stimuli.
  • Serum midkine levels are significantly higher in overweight/obese human subjects than in control subjects.
  • Midkine impairs insulin signaling in adipocytes from mice subjects.
  • Midkine activates the STAT3-SOCS3 pathway, a pathway that is critical in cytokine-induced insulin resistance.
  • Midkine could reduce insulin-stimulated translocation of GLUT4, a protein responsible for insulin-regulated glucose transport into the cell.
  • Midkine can weaken insulin signaling in adipocytes.

In conclusion, Midkine is a protein that could be a potential link between obesity and insulin resistance. This could offer a new target to treat insulin resistance and other obesity-related conditions.

Fan, N. et al. "Midkine, a Potential Link between Obesity and Insulin Resistance" PLOS one. 2014; 9(2): 1-10. Diabetes/Metabolism Research & Reviews 2014