title: Overexpression of Kruppel-like factor 7 regulates adipocytokine gene expressions in human adipocytes and inhibits glucose-induced insulin secretion in pancreatic beta-cell line.
abstract: We have identified Kruppel-like factor 7 (KLF7) as a new candidate for conferring susceptibility to type 2 diabetes. To ascertain the possible involvement of KLF7 in the pathogenesis of type 2 diabetes, we examined the functional roles of KLF7 in various types of cells. In human adipocytes overexpressing KLF7, the expression of adiponectin and leptin was decreased compared with that in control cells, whereas expression of IL-6 was increased. In the insulin-secreting cell line (HIT-T15 cells), the expression and glucose-induced secretion of insulin were significantly suppressed in KLF7-overexpressed cells compared with control cells, accompanied by the reduction in the expression of glucose transporter 2, sulfonylurea receptor 1, Kir6.2, and pancreatic-duodenal homeobox factor 1. We also found that the overexpression of KLF7 resulted in the decrease of hexokinase 2 expression in smooth muscle cells, and of glucose transporter 2 expression in the HepG2 cells. These results suggest that KLF7 may contribute to the pathogenesis of type 2 diabetes through an impairment of insulin biosynthesis and secretion in pancreatic beta-cells and a reduction of insulin sensitivity in peripheral tissues. Therefore, we suggest that KLF7 plays an important role in the pathogenesis of type 2 diabetes, and may be a useful target for new drugs to aid in the prevention and treatment of this disease.
authors.affiliation: Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research, Kanagawa 230-0045, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D007328:Insulin; C480503:KLF7 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D005947:Glucose