RT Journal Article T1 Glucokinase and Glucokinase Regulatory Proteins are Functionally Coexpressed before Birth in the Rat Brain A1 Roncero Rincón, Isabel A1 Sanz Miguel, María Del Carmen A1 Álvarez, E. A1 Barrio, P.A. A1 Blázquez Fernández, Enrique AB Our previous description of functional glucokinase (GK) isoforms and their interactions with glucokinase regulatory protein (GKRP) in adult rat and human brains suggested that both participate in glucose sensing in the central nervous system. To determine whether both proteins are coexpressed and active before birth or during early post-natal life, we characterised these molecules in the brains of foetal and post-natal pup rats. We found GK and GKRP mRNAs that were similar to those previously reported in the adult rat brain. Likewise, GK and GKRP gene expression gave rise to proteins of 52 and 69 kDa, respectively. Immunohistochemistry experiments showed the colocalisation of both GK and GKRP proteins in the same brain cells of 21-day-old rat foetuses. Furthermore, coprecipitation of GK and GKRP in the presence of fructose 6-phosphate suggests interactions between both proteins. The presence of GK phosphorylating activity was detected in different brain areas of 21-day-old foetuses with a contribution to the total glucose-phosphorylating activity of between 17.2 ± 1.7% and 12.4 ± 3.7%, with the hypothalamus being the region of maximum activity. The hypothalamic GK activity in 21-day-old foetuses has a high apparent Km for glucose and no product inhibition by glucose 6-phosphate. Our findings indicate that both proteins may be functionally active before birth and that they can act within a glucose sensor system involved in controlling food intake. PB Wiley SN 0953-8194 SN 1365-2826 YR 2009 FD 2009-11-18 LK https://hdl.handle.net/20.500.14352/112120 UL https://hdl.handle.net/20.500.14352/112120 LA eng NO Roncero I, Sanz C, Alvarez E, Vázquez P, Barrio PA, Blázquez E. Glucokinase and glucokinase regulatory proteins are functionally coexpressed before birth in the rat brain. J Neuroendocrinol. 2009 Dec;21(12):973-81. doi: 10.1111/j.1365-2826.2009.01919.x. NO Instituto de Salud Carlos III (España) NO Comunidad Autónoma de Madrid NO Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas NO Ministerio de Ciencia e Innovación (España) DS Docta Complutense RD 8 abr 2025