Insulin Action in Neuronal and Non-Neuronal Cells and the Regulation of Puberty  and Reproduction

Presentation Number: SUN 486
Date of Presentation: April 2nd, 2017

Iyad Manaserh*1, Jennifer Hill2 and Selin Longmire3
1University of Toledo, Toledo, 2University of Toledo Health Science campus, Toeldo, 3University of Toledo


Infertility is a major problem in the United States and occurs in approxiately 10% of reproductive aged women. Hyperinsulinemia and obesity are associated with infertility and reduced GnRH release. Bruning et al., 2000 demonstrated that male and female mice lacking insulin signaling in the brain (both neuronal and non-neuronal cells) during their development exhibit subfertility. However, the specific cell types mediating insulin effects on fertility remain unidentified. To determine whether hypothalamic insulin sensing plays an important role in the regulation of energy hemostasis and fertility, we generated mice lacking insulin receptors in astrocytes (GFAP-cre, IR flox-flox). Male and female GFAP-IR mice showed a delay in balanopreputial separation and vaginal opening and first estrous, respectively. Female GFAP-IR mice also exhibited longer estrus cycle lengths and irregular estrus cyclicity. Adult body weight, body growth and fat composition were comparable between the two groups. These data suggest that impaired insulin sensing in astrocytes delays the initiation of puberty and affects adult reproductive function. Additional investigation is needed into the mechanisms underlying these effects.


Nothing to Disclose: IM, JH, SL