Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) also known as CD66a , is a human gene. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Multiple cellular activities have bee ...
Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) also known as CD66a , is a human gene. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. CEACAM1, a substrate of insulin receptor in liver, regulates insulin action by promoting insulin clearance. Inactivation of CEACAM1 impairs insulin clearance and causes hyperinsulinemia, insulin resistance, dyslipidemia and visceral adiposity in transgenic mice. Thus, there is a strong association between visceral obesity, insulin resistance and reduced hepatic CEACAM1 level. PC-1 (plasma cell membrane glycoprotein-1), or ENPP1 (ectonucleotide pyrophosphatase/phosphodieterase) was originally described as a marker of terminally differentiated B cells within lymphoid system. It is an insulin receptor (IR) inhibitor that is elevated in cells and tissues of insulin-resistant humans. The suppression of PC-1/ENPP-1 expression improves insulin sensitivity in vitro and in vivo. The aim of this study is to determine whether the difference of CEACAM-1 and PC1 expression in liver, muscle, stomach, jejunum, abdominal fat between diabetics or non-diabetics.
Material and Methods: Liver, muscle, stomach, jejunum, abdominal fat tissue of 20 diabetics and 20 non-diabetics will be selected from the files of Wakefield GE research institute Diabetes group. Any project involving experimentation with human subjects or animals requires approval from appropriate hospital or animal ethical committees. Approval has been given by the Central Regional Ethics Committee (CEN/05/02/2004) for the collection and use of all tissue for this study.
The expression of CEACAM1 and PC-1 protein was determined by Immunohistochemical staining of formalin-fixed paraffin-embedded sections of each sample. The primary antibodies used were mouse monoclonal CEACAM1 (clone 29H2, Abcam, Cambridge,UK) and goat polyclonal ENPP1 (Abnova). Decreased expression of CEACAM1 was defined as negative staining in more than one third of hepatocytes. Overexpression of PC-1 was defined as positive staining in more than two third of hepatocytes. We statistically analyzed to compare the expression of CEACAM-1 and PC-1 in diabetics and non-diabetics groups.
Results: CEACAM1 and PC-1 were expressed in liver tissue but not expressed in muscle, stomach, jejunum and abdominal fat tissue. CEACAM1 was expressed in cannalicular pattern of hepatocytes. PC-1 was expressed in membranous pattern of hepatocytes. Decreased expression of CEACAM1 was noted in 7 (35%) of 20 diabetes and 5 (24%) of 20 non-diabetes. Overexpression of PC-1 was noted in 7 (35%) of 20 diabetes and 9 (45%) of 20 non-diabetes. There was no significant correlation between decreased expression of CEACAM1 or overexpression of PC-1 and presence of diabetes. Decreased expression of CEACAM1 was noted in 12 (38.7%) of 31 moderate or severe fatty liver and 0 (0%) of 8 non- or mild fatty liver. Overexpression of PC-1 was noted in 12 (38.7%) of 31 moderate or severe fatty liver and 4 (44.4%) of 9 non- or mild fatty liver. There was significant correlation between decreased expression of CEACAM1 and presence of moderate to severe fatty liver (p=0.026). There was no significant correlation between overexpression of PC-1 and presence of moderate to severe fatty liver.
Conclusion: Immunohistochemically, CEACAM1 or PC-1 expression between in diabetes and non-diabetes liver was not different. However, CEACAM1 expression was inversely correlated with severity of fatty liver. The result suggests the defect of insulin clearance by decreased expression of CEACAM1 might be associated with diabetic fatty liver as well as non-diabetic fatty liver