Overexpression of Angiopoietin-like protein 4 alters the protein expression profiles of the liver tissue in DB/DB diabetic mice

Abstract

Type 2 Diabetes Mellitus (T2DM) is one of the most common endocrine diseases worldwide. The prolonged hyperglycemia can cause many diabetic complications such as cardiovascular diseases and stroke, which are becoming the top cause of morbidity and mortality in the aging population. Recently, we have reported that angiopoietin-like protein 4 (ANGPTL4), a circulating protein predominantly produced from fat tissue and liver, can potently decrease blood glucose in db/db diabetic animal mice, possibly by acting through the liver tissue (PNAS, 2005, 102:6086 – 91). However, the molecular and cellular basis that underlies the liver actions of ANGPTL4 remains to be clarified. In this study, we have employed two-dimensional differential gel electrophoresis (2D-DIGE) technology to study the protein profiles in the livers of db/db diabetic mice treated with or without ANGPTL4. Our results demonstrated that, compared with those in the lean littermates, several enzymes involved in gluconeogenesis and lipid metabolism are increased while a lot of cytoskeletal proteins and chaperons are down regulated in db/db diabetic mice. Especially, several enzymes in the methionine/homocysteine metabolic cycle are significantly elevated, leading to the increased levels of S-adenosylmethionine, the methyl donor in virtually all known biological methylation reactions. On the other hand, ANGPTL4 treatment can reverse most of these protein changes in db/db mice. In addition, we have also found that ANGPTL4 can selectively modulate the expression of a lot of proteins that are involved in other biological pathways, such as inflammatory responses and cell growth, suggesting that this protein may possess other functions as well. In conclusion, our results support our previous finding that ANGPTL4, an emerging adipokine involved in energy metabolism, exert its actions through the liver tissue.