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

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.