5-aminoimidazole-4-carboxy-amide-1-beta-D-ribofuranoside treatment ameliorates hyperglycaemia and hyperinsulinaemia but not dyslipidaemia in KKAy-CETP mice

Diabetologia. 2001 Dec;44(12):2180-6. doi: 10.1007/s001250100027.

Abstract

Aim/hypothesis: 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).

Conclusion/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / therapeutic use*
  • Animals
  • Carrier Proteins / genetics
  • Cholesterol Ester Transfer Proteins
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Disease Models, Animal
  • Female
  • Glucose / biosynthesis
  • Glucose / pharmacokinetics
  • Glycoproteins*
  • Hyperglycemia / drug therapy*
  • Hyperinsulinism / drug therapy*
  • Hyperlipidemias / drug therapy
  • Hypoglycemic Agents / therapeutic use*
  • Mice
  • Mice, Transgenic / genetics
  • Muscle, Skeletal / metabolism
  • Ribonucleotides / therapeutic use*

Substances

  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Glycoproteins
  • Hypoglycemic Agents
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • AICA ribonucleotide
  • Glucose