Thyronamines are naturally occurring, chemical relatives of thyroid hormone. 
Systemic administration of synthetic 3-iodothyronamine (T(1)AM) and - to a 
lesser extent - thyronamine (T(0)AM), leads to acute bradycardia, hypothermia, 
decreased metabolic rate, and hyperglycemia. This profile led us to hypothesize 
that the central nervous system is among the principal targets of thyronamines. 
We investigated whether a low dose i.c.v. infusion of synthetic thyronamines 
recapitulates the changes in glucose metabolism that occur following i.p. 
thyronamine administration. Plasma glucose, glucoregulatory hormones, and 
endogenous glucose production (EGP) using stable isotope dilution were monitored 
in rats before and 120 min after an i.p. (50 mg/kg) or i.c.v. (0.5 mg/kg) bolus 
infusion of T(1)AM, T(0)AM, or vehicle. To identify the peripheral effects of 
centrally administered thyronamines, drug-naive rats were also infused 
intravenously with low dose (0.5 mg/kg) thyronamines. Systemic T(1)AM rapidly 
increased EGP and plasma glucose, increased plasma glucagon, and corticosterone, 
but failed to change plasma insulin. Compared with i.p.-administered T(1)AM, a 
100-fold lower dose administered centrally induced a more pronounced acute EGP 
increase and hyperglucagonemia while plasma insulin tended to decrease. Both 
systemic and central infusions of T(0)AM caused smaller increases in EGP, plasma 
glucose, and glucagon compared with T(1)AM. Neither T(1)AM nor T(0)AM influenced 
any of these parameters upon low dose i.v. administration. We conclude that 
central administration of low-dose thyronamines suffices to induce the acute 
alterations in glucoregulatory hormones and glucose metabolism following 
systemic thyronamine infusion. Our data indicate that thyronamines can act 
centrally to modulate glucose metabolism.