Despite a large number of studies, the role of melatonin on glucose metabol
ism is still controversial. The aim of the present work was to further char
acterize the effect of melatonin on insulin action during: i) intravenous i
nsulin tolerance test performed at different times of the day using melaton
in, a melatonin agonist (S-20304), a melatonin antagonist (S-20928) or in p
inealectomized rats, ii) euglycemic-hyperinsulinemic clamp performed in mel
atonin agonist-treated as well as in pinealectomized rats. The fall in glyc
emia after the insulin injection was not significantly affected by melatoni
n and melatonin agonist (S-20304) at ZT6, nor by the melatonin antagonist (
S-20928) at ZT13 nor in pinealectomized animals at ZT6 in comparison to the
ir respective control. Acute treatment with S-20304 or chronic suppression
of melatonin by pinealectomy did not significantly alter basal plasma gluco
se and insulin levels or hepatic glucose production and whole body or indiv
idual tissue glucose utilization. These data do not give support to a cruci
al role of melatonin on insulin action in normal rats.