title: Increased hepatic expression of dipeptidyl peptidase-4 in non-alcoholic             fatty liver disease and its association with insulin resistance and glucose metabolism.
abstract: Dipeptidyl peptidase-4 (DPP4) is a serine protease that degrades glucagon-like             peptide-1 (GLP-1), an incretin hormone that stimulates insulin secretion from             pancreatic β-cells. DPP4 is also involved in the regulation of T cell-mediated             inflammatory processes. These properties of DPP4 suggest that it may play a role             in the progression of non-alcoholic fatty liver disease (NAFLD). Hepatic DPP4             mRNA expression levels were analyzed by real-time PCR using liver biopsy samples             from 17 NAFLD patients and 10 healthy subjects. In NAFLD patients, we also examined             correlations between DPP4 expression levels and metabolic factors, including homeostasis             model assessment-insulin resistance (HOMA-IR), body mass index (BMI), and serum             cholesterol and triglyceride levels. To examine the potential effects of nutritional             factors, DPP4 expression levels were analyzed in HepG2 cells subjected to various             culture conditions. Hepatic DPP4 mRNA expression was significantly greater in             NAFLD patients than in control subjects. DPP4 expression levels were negatively             correlated with HOMA-IR and positively correlated with serum cholesterol levels.             In HepG2 cells, high glucose significantly enhanced DPP4 expression, whereas insulin,             fatty acids and cholesterol did not. Increased hepatic expression of DPP4 in NAFLD             may be associated with metabolic factors, including insulin resistance, and may             adversely affect glucose metabolism in this liver disease.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mmasayuki@med.kyushu-u.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D002784:Cholesterol; D018819:Dipeptidyl Peptidase 4; D005947:Glucose