title: Cell biology of diabetic kidney disease.
abstract: In large part cellular dysfunctions induced by chronic hyperglycemia are similar in type-1 and -2 diabetes. In both instances chronic hyperglycemia induces injury to a multitude of organs by affecting various target cells. The cells affected may include those derived from of epithelial or mesenchymal progenitors; and at times hyperglycemia may induce phenotypic changes with epithelial-mesenchymal transformation. In the majority of target cells the high-glucose ambience activates various intracellular pathways that are similar except for minor exceptions that are related to the selective expression of various molecules in a given cell type. Keeping in perspective a common paradigm applicable to most of the cells, a brief discussion of different hyperglycemia-induced cellular events pertaining to various pathways is described in this review. They include fluxes of glucose intermediaries in various cellular metabolic pathways, generation of advanced glycation end products (AGEs) and their extra- and intracellular effects, the role of protein kinase C, transforming growth factor-beta, guanosine triphosphate-binding proteins and reactive oxygen species (ROS) in various cellular signaling events. The latter, i.e., ROS, may be central to several intracellular pathways and modulate various events in a reciprocal manner. The information compiled under various subtitles of this synopsis is derived from an enormous amount of literature data summarized in several recent excellent reviews, and thus further reading of them is suggested to gather detailed comprehensive information on each of the subjects.
authors.affiliation: Department of Pathology, Northwestern University School of Medicine, Chicago, Ill 60611, USA. y-kanwar@northwestern.edu
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Kanwar
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akagi
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Baibaswata
authors.initials: B
authors.lastname: Nayak
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Sumant S
authors.initials: SS
authors.lastname: Chugh
authors.forename: Farhad R
authors.initials: FR
authors.lastname: Danesh
mesh_terms: D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*