title: Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration.
abstract: Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9-18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulin-dependent diabetes.
authors: Center for Neuroscience and Cell Biology, Dept. of Life Sciences, Univ. of Coimbra, Largo Marquês de Pombal, 3004 - 517, Coimbra, Portugal.
authors: Ana F
authors: AF
authors: Soares
authors: Rui A
authors: RA
authors: Carvalho
authors: Francisco J
authors: FJ
authors: Veiga
authors: Marco G
authors: MG
authors: Alves
authors: Fátima O
authors: FO
authors: Martins
authors: Ivan
authors: I
authors: Viegas
authors: Juan D
authors: JD
authors: González
authors: Isidoro
authors: I
authors: Metón
authors: Isabel V
authors: IV
authors: Baanante
authors: John G
authors: JG
authors: Jones
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005941:Glucokinase / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000096:biosynthesis*; D007328:Insulin / Q000008:administration & dosage*; D050155:Lipogenesis / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D005941:Glucokinase