title: Fructose and uric acid in diabetic nephropathy.
abstract: Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.forename: Takuji
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Diana
authors.initials: D
authors.lastname: Jalal
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.forename: Janet K
authors.initials: JK
authors.lastname: Snell-Bergeon
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D003928:Diabetic Nephropathies / Q000473:pathology*; D004195:Disease Models, Animal; D005632:Fructose / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D011687:Purines / Q000737:chemistry; D051381:Rats; D014527:Uric Acid / Q000097:blood* / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D011687:Purines; D014527:Uric Acid; D005632:Fructose; D000255:Adenosine Triphosphate