Figure 5. Liver Kisspeptin1 expression and plasma kisspeptin levels are elevated in mouse models of DM and in humans with T2DM.

A (top) qRT-PCR for Kiss1 in liver tissue; and (bottom) liver IB for kisspeptin1 in SD, HFD fed and Lepr^db/db mice. Both Kiss1 mRNA and kisspepetin1 protein are increased in HFD fed mice and found at higher levels in db/db mouse livers (mean±SEM, *P<0.05).

B Plasma kisspeptin1 in SD, HFD fed and Lepr^db/db mice. Plasma kisspeptin1 is increased in (left) HFD fed and (right) in Lepr^db/db mice as compared to SD fed littermates (mean±SEM, *P<0.05).

C GSIS from cultured (left) Kiss1R^fl/fl and (right) Panc-ΔKiss1R mouse islets in media conditioned with plasma from HFD fed and Lepr^db/db mice. GSIS from Kiss1R^fl/fl is suppressed during culture in media conditioned with HFD fed or db/db plasma at 1:10 dilution but not at 1:100 dilution. GSIS from Panc-ΔKiss1R islets is unaffected by media conditioned with plasma of HFD fed or Lepr^db/db mice (mean±SEM, *P<0.05).

D Representative liver IB for kisppeptin1 in humans without DM and humans with T2DM. Humans with T2DM exhibit varying degrees of kisspeptin immunoreactivity in liver tissue.

E Plasma kisspeptin1 in humans without DM and with T2DM. Plasma kisspeptin1 levels are elevated in humans with T2DM as compared to humans without diabetes (mean±SEM, *P<0.05).

F GSIS from cultured (left) Kiss1R^fl/fl and (right) Panc-ΔKiss1R mouse islets in media conditioned with plasma from humans with T2DM and without DM. GSIS from Kiss1R^fl/fl but not from Panc-ΔKiss1R islets is suppressed during culture in media conditioned with T2DM plasma (mean±SEM, *P<0.05).