title: Restoration of hepatic glycogen deposition reduces hyperglycaemia, hyperphagia and gluconeogenic enzymes in a streptozotocin-induced model of diabetes in rats.
abstract: OBJECTIVE
  Glycogen deposition is impaired in diabetes, thus contributing to the development of hyperglycaemia. Several glucose-lowering strategies have attempted to increase liver glycogen deposition by modulating targets, which eventually trigger the activation of liver glycogen synthase (LGS). However, these targets also alter several other biological processes, and therefore their therapeutic use may be limited. Here we tested the approach of directly activating LGS and evaluated the potential of this strategy as a possible treatment for diabetes.
  
  
  METHODS
  In this study, we examined the efficacy of directly overproducing a constitutively active form of LGS in the liver to ameliorate streptozotocin-induced diabetes in rats.
  
  
  RESULTS
  Activated mutant LGS overproduction in the liver of streptozotocin-induced diabetic rats normalised liver glycogen content, despite low levels of glucokinase and circulating insulin. Moreover, this overproduction led to a decrease in food intake and in the production of the main gluconeogenic enzymes, glucose-6-phosphatase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The resulting combined effect was a reduction in hyperglycaemia.
  
  
  CONCLUSIONS
  The restoration of liver glycogen ameliorated diabetes and therefore is considered a potential strategy for the treatment of this disease.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ros
authors.forename: M
authors.initials: M
authors.lastname: García-Rocha
authors.forename: J
authors.initials: J
authors.lastname: Calbó
authors.forename: J J
authors.initials: JJ
authors.lastname: Guinovart
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000628:therapy*; D004435:Eating / Q000235:genetics / Q000502:physiology; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D006006:Glycogen Synthase; D006597:Fructose-Bisphosphatase; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP)