Dietary Exposure to Transgenic Rice Expressing the Spider Silk Protein Fibroin Reduces Blood Glucose Levels in Diabetic Mice: The Potential Role of Insulin Receptor Substrate-1 Phosphorylation in Adipocytes

Ji-Eun Park; Yeon Jae Jeong; Joon Beom Park; Hye Young Kim; Young Hyun Yoo; Kwang Sik Lee; Won Tae Yang; Doh Hoon Kim; Jong-Min Kim

doi:10.12717/DR.2019.23.3.223

Dietary Exposure to Transgenic Rice Expressing the Spider Silk Protein Fibroin Reduces Blood Glucose Levels in Diabetic Mice: The Potential Role of Insulin Receptor Substrate-1 Phosphorylation in Adipocytes

Dev Reprod. 2019 Sep;23(3):223-229. doi: 10.12717/DR.2019.23.3.223. Epub 2019 Sep 30.

Authors

Ji-Eun Park¹, Yeon Jae Jeong¹, Joon Beom Park¹, Hye Young Kim¹, Young Hyun Yoo¹, Kwang Sik Lee², Won Tae Yang², Doh Hoon Kim², Jong-Min Kim¹

Affiliations

¹ Dept. of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 49201, Korea.
² College of Life Sciences and Natural Resources, Dong-A University, Busan 49315, Korea.

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR). T2DM is correlated with obesity and most T2DM medications have been developed for enhancing insulin sensitivity. Silk protein fibroin (SPF) from spiders has been suggested as an attractive biomaterial for medical purposes. We generated transgenic rice (TR) expressing SPF and fed it to diabetic BKS.Cg-m+/+Lepr^db mice to monitor the changes in blood glucose levels and adipose tissue proteins associated with energy metabolism and insulin signaling. In the present study, the adipocyte size in abdominal fat in TR-SPF-fed mice was remarkably smaller than that of the control. Whereas the adenosine monophosphate-activated protein kinase (AMPK)-activated protein kinase and insulin receptor substrate 1 (IRS1) protein levels were increased in abdominal adipose tissues after TR-SPF feeding, levels of six-transmembrane protein of prostate 2 (STAMP2) proteins decreased. Phosphorylation of AMPK at threonine 172 and IRS1 at serine 307 and tyrosine 632 were both increased in adipose tissues from TR-SPF-fed mice. Increased expression and phosphorylation of IRS1 at both serine 307 and tyrosine 632 in adipose tissues indicated that adipocytes obtained from abdominal fat in TR-SPF-fed mice were more susceptible to insulin signaling than that of the control. STAMP2 protein levels decreased in adipose tissues from TR-SPF-fed mice, indicating that STAMP2 proteins were reducing adipocytes that were undergoing lipolysis. Taken together, this study showed that TR-SPF was effective in reducing blood glucose levels in diabetic mice and that concurrent lipolysis in abdominal adipocytes was associated with alterations of AMPK, IRS1, and STAMP2. Increased IRS1 expression and its phosphorylation by TR-SFP were considered to be particularly important in the induction of lipolysis in adipocytes, as well as in reducing blood glucose levels in this animal model.

Keywords: Adipocytes; Diabetic mouse; IRS1; Spider silk protein fibroin; Transgenic rice.