Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus).
Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish.
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.|Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Ayelén Melisa
AM
Blanco
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.|Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús, Buenos Aires, Argentina.
Juan Ignacio
JI
Bertucci
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Naresh
N
Ramesh
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
María Jesús
MJ
Delgado
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
Ana Isabel
AI
Valenciano
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Suraj
S
Unniappan
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006054:Goldfish / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*
D054439:Ghrelin; D051273:Glucose Transporter Type 2; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D005947:Glucose