title: The GK rat beta-cell: a prototype for the diseased human beta-cell in type 2 diabetes?
abstract: Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of type 2 diabetes (T2D) mellitus. Nowadays, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased beta-cell number, impaired beta-cell function, and their multifactorial aetiologies. This review is aimed to illustrate to what extend the Goto-Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved be a valuable tool offering sufficient commonalities to study these aspects. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of multiple pathogenic players: (i) several independent loci containing genes responsible for some diabetic traits (but not decreased beta-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased beta-cell neogenesis and/or proliferation) which is transmitted to the next generation; and (iii) loss of beta-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammatory mediators, oxidative stress and to perturbed islet microarchitecture.
authors.affiliation: Groupe Biologie et Pathologie du Pancréas Endocrine, Laboratoire de Physiopathologie de la Nutrition, UMR CNRS 7059, Université Paris-Diderot/UP7, Paris, France. portha@univ-paris-diderot.fr
authors.forename: B
authors.initials: B
authors.lastname: Portha
authors.forename: G
authors.initials: G
authors.lastname: Lacraz
authors.forename: M
authors.initials: M
authors.lastname: Kergoat
authors.forename: F
authors.initials: F
authors.lastname: Homo-Delarche
authors.forename: M-H
authors.initials: MH
authors.lastname: Giroix
authors.forename: D
authors.initials: D
authors.lastname: Bailbé
authors.forename: M-N
authors.initials: MN
authors.lastname: Gangnerau
authors.forename: M
authors.initials: M
authors.lastname: Dolz
authors.forename: C
authors.initials: C
authors.lastname: Tourrel-Cuzin
authors.forename: J
authors.initials: J
authors.lastname: Movassat
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D051381:Rats