5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice

Diabetologia. 2002 Jan;45(1):56-65. doi: 10.1007/s125-002-8245-8.


Aims/hypothesis: The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.

Methods: Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days.

Results: Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal.

Conclusion/interpretation: The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / administration & dosage
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology*
  • Animals
  • Biological Transport / drug effects
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Glycogen / metabolism
  • Homeostasis / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Injections, Subcutaneous
  • Insulin / blood
  • Insulin Resistance*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Glycogen / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Obesity*
  • Ribonucleotides / administration & dosage
  • Ribonucleotides / pharmacology*


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Liver Glycogen
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Glycogen
  • AICA ribonucleotide
  • Glucose