1 The effect of chronic saccharin (benzosulphimide) consumption on glu
cose homeostasis was examined in normal lean +/+ mice and genetically
obese hyperglycaemic insulin-resistant ob/ob mice. 2 Consumption of a
5% (w/v) sodium saccharin solution for 7 weeks prevented the developme
nt of hyperglycaemia, improved glucose tolerance (area under curve dec
reased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and
reduced excessive weight gain (by 18%) in ob/ob mice. 3 Consumption of
5% (w/v) sodium saccharin temporarily decreased hyperphagia at the be
ginning of treatment, decreased hepatic glycogen content (by 47%), inc
reased abdominal muscle glycogen content (by 82%), but did not signifi
cantly alter the hypoglycaemic response to exogenous insulin in ob/ob
mice. 4 Consumption of a 1% (w/v) sodium saccharin solution did not pr
event the development of hyperglycaemia in ob/ob mice. 5 Normal lean /+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal
decrease (by 8%) in glycaemia, and glucose tolerance was improved (ar
ea under curve decreased by 30%) without a significant change in the i
nsulin response to glucose or the hypoglycaemic effect of exogenous in
sulin. 6 The results suggest that chronic consumption of saccharin can
defer the development of hyperglycaemia and improve glucose homeostas
is in insulin-resistant ob/ob mice through a mechanism that is indepen
dent of insulin.