Glucose homeostasis is altered in Kiss1-GABAB1KO adult male mice.

SURKIN PN; LIBERTUN C; DI GIORGIO NP ; REPETTO E; LUX LANTOS VAR; BIZZOZZERO HIRIART M; BETTLER B

Modalidad virtual

Congreso; IV Reunión Conjunta de Sociedades de Biología de la República Argentina; 2020

Kisspeptin (Kiss1) neurons co-express GABAB receptors (GABABR) and GABA is an important regulator of their physiology. Kiss1 expression is a key factor in the control of reproduction and is involved in metabolic control. We developed a new strain of mice with specific deletion of GABAB1R in Kiss1 cells/neurons (KO). KO males have similar body weight compared to WT; however, they have an increase in postnatal ano-genital index (AGI), increase in arcuate and decrease in anteroventral periventricular nucleus Kiss1 expression. Here, we confirmed the specific deletion of GABAB1R by double immunofluorescence and we determined different parameters in WT and KO adult males: a) AGI and fertility; b) non-fasted (NFG) and fasted (FG) glycaemia; c) glucose (GTT) and insulin (ITT) tolerance tests. AGI and fertility in KO were similar between genotypes. While KO males had normal NFG, they had higher FG, altered response to glucose (GTT) and lower insulin sensitivity (ITT). In conclusion, the lack of GABABR in Kiss1 cells alters glucose homeostasis in adult male mice. We need to investigate whether these alterations have a central or peripheral origin, or both. (CONICET/ANPCYT/ISN-CAEN/UBA/ René Barón F./ Williams F.)