title: High-fat diet feeding significantly attenuates anagliptin-induced regeneration of islets of Langerhans in streptozotocin-induced diabetic mice.
abstract: BACKGROUND
  DPP-4 inhibitors reportedly exert effects on both alpha and beta cells, and promote the proliferation and survival of beta cells. We investigated the effects of anagliptin on structurally-impaired islets of Langerhans in streptozotocin (STZ)-treated mice, fed either a normal or a high-fat diet. Pdx-1 expression in the pancreas and serum insulin/glucagon concentrations were also examined.
  
  
  RESULTS
  Anagliptin treatment significantly up-regulated pancreatic Pdx-1 expression, with elevated serum glucagon-like peptide-1 concentrations, regardless of whether the diet was normal or high-fat. However, interestingly, the beta cell regeneration, structural normalization of islets of Langerhans including alpha cell: beta cell area ratios, and serum insulin elevation, all observed with anagliptin administration in the animals fed a normal diet, were markedly suppressed in the high-fat fed group.
  
  
  CONCLUSIONS
  High-fat diet feeding clearly weakened the regenerative effects of anagliptin on the islets of Langerhans in STZ-treated mice. Our findings suggest the importance of normalizing lipid metabolism for full manifestation of DPP-4 inhibitor effects on the islets of Langerhans.
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Fukuoka, Higashi-ku Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Shinjo
authors.affiliation: Division of Molecular Medical Science, Department of Medical Chemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Minami-ku 734-8551 Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Fukuoka, Higashi-ku Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Iwashita
authors.affiliation: Division of Cervico-Gnathostomatology, Department of Dental Science for Health Promotion, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, Bunkyo-ku Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1 Oyaguchikami-machi, Tokyo, Itabashi-ku Japan.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.affiliation: Division of Diabetes and Metabolism, Institute for Adult Disease, Asahi Life Foundation, 1-6-1 Marunouchi, Tokyo, Chiyoda-ku Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo, Bunkyo-ku Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Section of Periodontology, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Fukuoka, Higashi-ku Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.affiliation: Division of Molecular Medical Science, Department of Medical Chemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Minami-ku 734-8551 Japan.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
keywords: Anagliptin; DPP-4 inhibitor; High-fat diet; Islet of Langerhans; Streptozotocin