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Hepatic Steatosis Alleviated in Diabetic Mice upon Dietary Exposure to Fibroin via Transgenic Rice: Potential STAMP2 Involvement in Hepatocytes

발생과생식 2020년 24권 3호 p.231 ~ 239
박지은, 정연재, 김혜영, 유영현, 이광식, 양원태, 김도훈, 김종민,
소속 상세정보
박지은 ( Park Ji-Eun ) - Dong-A University College of Medicine Department of Anatomy and Cell Biology
정연재 ( Jeong Yeon-Jae ) - Dong-A University College of Medicine Department of Anatomy and Cell Biology
김혜영 ( Kim Hye-Young ) - Dong-A University College of Medicine Department of Anatomy and Cell Biology
유영현 ( Yoo Young-Hyun ) - Dong-A University College of Medicine Department of Anatomy and Cell Biology
이광식 ( Lee Kwang-Sik ) - Dong-A University College of Life Science and Natural Resources
양원태 ( Yang Won-Tae ) - Dong-A University College of Life Science and Natural Resources
김도훈 ( Kim Doh-Hoon ) - Dong-A University College of Life Science and Natural Resources
김종민 ( Kim Jong-Min ) - Dong-A University College of Medicine Department of Anatomy and Cell Biology

Abstract


Many benefits of silk protein fibroin (SPF) have been suggested in biomedical applications; and notably, significant SPF effects have been observed for metabolic syndromes that are directly linked to insulin resistance, such as type 2 diabetes mellitus (T2DM). Based on our previous findings, we believe that SPF from spiders exhibits outstanding glucose-lowering effects in diabetic BKS.Cg-m+/+Leprdb mice. In order to evaluate the dietary effects of SPF in diabetic animals, we generated several lines of transgenic rice (TR) that expresses SPF, and the feeding of TR-SPF to diabetic animals decreased blood glucose levels, but did not change insulin levels. Western blot analyses of hepatic proteins showed that AMP-activated protein kinase (AMPK) expression and phosphorylation both decreased in TR-SPF-fed groups, compared with controls. This finding suggests that the glucose-lowering effects in this diabetic animal model might be AMPK-independent. In contrast, six-transmembrane protein of prostate 2 (STAMP2) was upregulated after TR-SPF exposure. Together with STAMP2, the Akt protein phosphorylation increased after TR-SPF exposure, which indicates that STAMP2 leads to Akt phosphorylation and thus increases insulin sensitivity in hepatocytes.
Importantly, the hepatic steatosis that was seen in the liver of diabetic mice was remarkably alleviated in TR-SPF-fed mice. Hepatocytes that were immunopositive for STAMP2 were overwhelmingly observed in hepatic tissues from TR-SPF-fed mice compared to the control.
Taken together, these results suggest that feeding diabetic mice with TR-SPF upregulates STAMP2 expression and increases Akt phosphorylation in hepatic tissues and thus potentially alleviates insulin resistance and hepatic steatosis.

키워드

Spider silk protein fibroin; Six-transmembrane protein of prostate 2 (STAMP2); Hepatocytes; Hepatic steatosis; Diabetic mouse

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