title: 5-aminoimidazole-4-carboxy-amide-1-beta-D-ribofuranoside treatment ameliorates hyperglycaemia and hyperinsulinaemia but not dyslipidaemia in KKAy-CETP mice.
abstract: OBJECTIVE
  5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside increases 5'-AMP-activated kinase activity in insulin-sensitive tissues known to control glucose homeostasis. We hypothesised that 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside treatment could have a beneficial effect on glucose homeostasis in KKAy-CETP mice, a model of Type II (non-insulin-dependent) diabetes mellitus. Our aim was to examine potential effects of acute and chronic (7-day) 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside treatment on glucose homeostasis in KKAy-CETP diabetic mice.
  
  
  METHODS
  Female KKAy-CETP mice were treated with 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside by a single daily injection for 7 days (100, 300, or 500 mg. kg-1. day-1).
  
  
  RESULTS
  After 7 days of treatment with 500 mg. kg-1. day-1 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside, blood glucose and plasma insulin concentrations were reduced (p < 0.01). Body weight and food intake were also reduced after treatment (p < 0.01 and p < 0.05, respectively). Glucose and insulin tolerance were improved (p < 0.05), whereas endogenous glucose production was suppressed (p < 0.05). The beneficial effect of 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside on hyperglycaemia and hyperinsulinaemia was due to an inhibition of endogenous glucose production, since in vivo and in vitro basal and insulin-stimulated glucose uptake in skeletal muscle was not affected by 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside. Other features of the treatment included increased plasma of free fatty acid concentration (1.9-fold, p < 0.01) and triglycerides (1.3-fold, p < 0.05).
  
  
  CONCLUSIONS
  5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside treatment attenuated hyperglycaemia and hyperinsulinaemia but not dyslipidaemia in KKAy-CETP mice, a model of Type II diabetes. The blood glucose lowering effects of 5-aminoimidazole-4-carboxy-amide-1-beta-d-ribofuranoside occurs mainly as a consequence of reduced endogenous glucose production because insulin-stimulated skeletal muscle glucose uptake has not been altered.
authors.affiliation: Department of Pharmacology, Biovitrum, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Fiedler
authors.forename: J R
authors.initials: JR
authors.lastname: Zierath
authors.forename: G
authors.initials: G
authors.lastname: Selén
authors.forename: H
authors.initials: H
authors.lastname: Wallberg-Henriksson
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: K S
authors.initials: KS
authors.lastname: Sakariassen
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000096:biosynthesis / Q000493:pharmacokinetics; D006023:Glycoproteins; D006943:Hyperglycemia / Q000188:drug therapy*; D006946:Hyperinsulinism / Q000188:drug therapy*; D006949:Hyperlipidemias / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D012265:Ribonucleotides / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose