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Int J Clin Exp Pathol 2010;3(3):254-264
Original Article
miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by
repressing myotrophin (V1) protein expression
Yan Li, Xuejuan Xu, Ying Liang, Shanying Liu, Huisheng Xiao, Feng Lia Hu Chenga, Zuzhi Fu
Department of Endocrinology, The Second Affiliated Hospital,Sun Yat-Sen University,, and Department of Endocrinology, The First Affiliated
Hospital in Foshan Sun Yat-Sen University, Guangzhou, China.
Received December 29, 2009; accepted January, 2010; available online January, 2010
Abstract: Lipoapoptosis of pancreatic β cells caused by elevated circulating free fatty acids (FFAs) has now been recognized to be a pivotal
factor contributing to β cellular dysfunction and mass lose in type 2 diabetes. Although recent studies suggested an important role for the
ceramide pathway in the late destructive phase of lipid overload in the pancreatic β cells, the overall underlying mechanisms of lipoapoptosis,
however, remained poorly understood. mir-375 was recently characterized to be a pancreatic islet-specific miRNA implicated in the regulation of
insulin secretion and β-mass turnover. In the present study we further examined its effect on palmitate-induced lipoapoptosis in NIT-1 cells, a
NOD-derived β cell line. It was found that NIT-1 cells with ectopic mir-375 expression were much more susceptible to palmitate-induced
lipoapoptosis. In contrast, knockdown of endogenous pri-miRNA 375 expression by a modified antisense oligo, 2′-O-me-375, almost
completely protected NIT-1 cells from palmitate-induced lipoapoptosis. We further demonstrated that mir-375 could target V1 mRNA
and repress its translation. Consistent with this assumption, NIT-1 cells transfected with 2′-O-me-375 showed significant higher levels of V1
protein after palmitate induction. Together, our data suggest that mir-375 could be a potential therapeutic target for prevention and intervention
of β-cell dysfunction and mass lose in type 2 diabetes. (IJCEP912009).
Key words: Lipoapoptosis, mir-375, NIT-1 cells, β-cell dysfunction, type 2 diabetes
Full text PDF
Address all correspondence to:
Yan Li, MD
Department of Endocrinology
The Second Affiliated Hospital, Sun Yat-Sen University
107th Yanjiang Western Road, Guangzhou 510120, China
Tel.: +86 20 81332286; fax: +86 20 81332404
E-mail address: liyan19642002@yahoo.cn
Original Article
miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by
repressing myotrophin (V1) protein expression
Yan Li, Xuejuan Xu, Ying Liang, Shanying Liu, Huisheng Xiao, Feng Lia Hu Chenga, Zuzhi Fu
Department of Endocrinology, The Second Affiliated Hospital,Sun Yat-Sen University,, and Department of Endocrinology, The First Affiliated
Hospital in Foshan Sun Yat-Sen University, Guangzhou, China.
Received December 29, 2009; accepted January, 2010; available online January, 2010
Abstract: Lipoapoptosis of pancreatic β cells caused by elevated circulating free fatty acids (FFAs) has now been recognized to be a pivotal
factor contributing to β cellular dysfunction and mass lose in type 2 diabetes. Although recent studies suggested an important role for the
ceramide pathway in the late destructive phase of lipid overload in the pancreatic β cells, the overall underlying mechanisms of lipoapoptosis,
however, remained poorly understood. mir-375 was recently characterized to be a pancreatic islet-specific miRNA implicated in the regulation of
insulin secretion and β-mass turnover. In the present study we further examined its effect on palmitate-induced lipoapoptosis in NIT-1 cells, a
NOD-derived β cell line. It was found that NIT-1 cells with ectopic mir-375 expression were much more susceptible to palmitate-induced
lipoapoptosis. In contrast, knockdown of endogenous pri-miRNA 375 expression by a modified antisense oligo, 2′-O-me-375, almost
completely protected NIT-1 cells from palmitate-induced lipoapoptosis. We further demonstrated that mir-375 could target V1 mRNA
and repress its translation. Consistent with this assumption, NIT-1 cells transfected with 2′-O-me-375 showed significant higher levels of V1
protein after palmitate induction. Together, our data suggest that mir-375 could be a potential therapeutic target for prevention and intervention
of β-cell dysfunction and mass lose in type 2 diabetes. (IJCEP912009).
Key words: Lipoapoptosis, mir-375, NIT-1 cells, β-cell dysfunction, type 2 diabetes
Full text PDF
Address all correspondence to:
Yan Li, MD
Department of Endocrinology
The Second Affiliated Hospital, Sun Yat-Sen University
107th Yanjiang Western Road, Guangzhou 510120, China
Tel.: +86 20 81332286; fax: +86 20 81332404
E-mail address: liyan19642002@yahoo.cn
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