LUTI: a double-function inhibitor isolated from naked flax seeds.

Lei Wang, Yinglu Chen, Feng Wu,Shasha Wu,Xiaojun Hu,Yawei Shi

ACTA BIOCHIMICA ET BIOPHYSICA SINICA(2019)

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摘要
Acute glucose fluctuation during the postprandial period causes a risk for type 2 diabetes mellitus (T2DM). alpha-Glucosidase inhibitors have been approved as therapeutic agents for diabetes. In the present study, a protein with alpha-glucosidase inhibitory activity from Flax (Linum usitatissimum) seeds was isolated using a one-step purification with Q-Sepharose4B column, followed by Sephacryl S-200 size-exclusion chromatography. It was identified as a trypsin inhibitor, named L. usitatissimum trypsin inhibitor (LUTI). The half maximal inhibitory concentration (IC50) of LUTI was 113.92 mu M for alpha-glucosidase and 6.17 mu M for trypsin. Lineweaver-Burk kinetic experiment showed that the protein exhibited two distinct inhibitory modes, a competitive inhibitor type for a-glucosidase and a non-competitive type for trypsin. The interaction between LUTI and alpha-glucosidase was detected through gel filtration chromatography and dynamic light scattering. Increased glucose consumption and lactic acid production were also observed following LUTI treatment in Caco-2 and HepG2 cells. LUTI inhibits not only the activity of trypsin but also the activity of alpha-glucosidase. It is expected that LUTI will become an oral hypoglycemic polypeptide drug for T2DM.
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关键词
alpha-glucosidase inhibitor,bifunctional inhibitor,LUTI,protein expression
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