title: Over-expression of muscle glycogen synthase in human diabetic nephropathy.
abstract: Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, but deterioration of renal function also correlates with tubular alterations. Human DN is characterized by glycogen accumulation in tubules. Although this pathological feature has long been recognized, little information exists about the triggering mechanism. In this study, we detected over-expression of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced expression suggests the participation of MGS in renal metabolic changes associated with diabetes. HK2 human renal cell line exhibited an intrinsic ability to synthesize glycogen, which was enhanced after over-expression of protein targeting to glycogen. A correlation between increased glycogen amount and cell death was observed. Based on a previous transcriptome study on human diabetic kidney disease, significant differences in the expression of genes involved in glycogen metabolism were analyzed. We propose that glucose, but not insulin, is the main modulator of MGS activity in HK2 cells, suggesting that blood glucose control is the best approach to modulate renal glycogen-induced damage during long-term diabetes.
authors.affiliation: Facultad de Medicina, Universidad San Sebastián, Puerto Montt, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Gatica
authors.forename: Romina
authors.initials: R
authors.lastname: Bertinat
authors.forename: Pamela
authors.initials: P
authors.lastname: Silva
authors.forename: Pamela
authors.initials: P
authors.lastname: Kairath
authors.forename: Felipe
authors.initials: F
authors.lastname: Slebe
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.forename: María J
authors.initials: MJ
authors.lastname: Ramírez
authors.forename: Juan C
authors.initials: JC
authors.lastname: Slebe
authors.forename: José M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
authors.forename: Carme
authors.initials: C
authors.lastname: Caelles
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Yáñez
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006006:Glycogen Synthase / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009132:Muscles / Q000201:enzymology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006006:Glycogen Synthase