Figure 2. Glucagon and insulin counter-regulate liver Kiss1 expression.

A qRT-PCR of Kiss1 and Pck1 in isolated mouse hepatocytes exposed to indicated treatment. Glucagon stimulates, insulin suppresses both genes (mean±SEM, *P<0.05).

B qRT-PCR of Kiss1 in isolated mouse hepatocytes exposed to vehicle (DMSO) or fsk/IBMX. cAMP stimulation stimulates Kiss1 expression (mean±SEM, *P<0.05)..

C Representative IB of cultured mouse hepatocytes after treatment with PBS, glucagon, insulin or INS plus GCGN. Glucagon stimulates kisspeptin, insulin treatment has little effect on already low kisspeptin. Insulin counterregulates glucagon stimulation of kisspeptin.

D qRT-PCR of Kiss1 in liver tissue of WT mice after in vivo ip treatment with vehicle (PBS) or glucagon. Glucagon treatment stimulates Kiss1 in liver (mean±SEM, *P<0.05).

E Representative liver IB in WT mice after in vivo ip treatment with PBS or glucagon. Glucagon increases liver kisspeptin1 (mean±SEM, *P<0.05).

F qRT-PCR of Kiss1 in liver of ad lib fed, O/N fasted, and refed WT mice. Fasting stimulates liver Kiss1 expression, refeeding supresses elevated Kiss1 (mean±SEM, *P<0.05).

G Liver IB from ad lib fed, O/N fasted, and refed WT mice. Fasting stimulates liver kisspeptin1.

H qRT-PCR of Kiss1 in liver of L-ΔGcgr mice after ip PBS or glucagon. Glucagon does to stimulate Kiss1 in L-ΔGcgr mice (mean±SEM, * P<0.05).

I (top) Representative liver IB from Gcgr^fl/fl and L-ΔGcgr mice. L-ΔGcgr lack GCGR. (bottom) Liver IB from Gcgr^fl/fl and L-ΔGcgr mice after ip treatment with PBS or glucagon. Baseline kisspeptin1 is similar in Gcgr^fl/fl and L-ΔGcgr mouse liver. Glucagon treatment stimulates kisspeptin1 in Gcgr^fl/fl but not in L-ΔGcgr mice.

J qRT-PCR of Kiss1 in liver of ad lib fed and O/N fasted L-ΔGcgr mice. O/N fast does not stimulate Kiss1 in L-ΔGcgr mouse liver (mean±SEM, *P<0.05).

K Representative liver IB from ad lib fed and O/N fasted Gcgr^fl/fl and L-ΔGcgr mice. Baseline kisspeptin1 is similar in Gcgr^fl/fl and L-ΔGcgr livers. Fasting stimulates kisspeptin1 in Gcgr fl/fl but not in L-ΔGcgr liver.

L qRT-PCR of Kiss1 in liver of Insr^fl/fl and L-ΔInsr mice. Liver Insr ablation does not affect Kiss1 expression (mean±SEM, *P<0.05).

M Representative liver IB of Insr^fl/fl and L-ΔInsr mice. L-ΔInsr liver lacks insulin receptor immunoreactivity.

N qRT-PCR of Kiss1 in liver of Insr^fl/fl and L-ΔInsr mice after ip treatment with vehicle PBS or glucagon. Glucagon stimulates Kiss1 in Insr^fl/fl mice and more so in L-ΔInsr liver (mean±SEM, *P<0.05).

O Representative liver IB of Insr^fl/fl and L-ΔInsr mice after ip PBS or glucagon. Glucagon stimulates stronger liver kisspeptin1 production in L-ΔInsr than in Insr^fl/fl liver.