Is the canine corpus luteum an insulin-sensitive tissue?
This study aimed to determine in the canine corpus luteum throughout the dioestrus (1) the influence of insulin on glucose uptake; (2) the regulation of genes potentially involved; and (3) the influence of hypoxia on glucose transporter expression and steroidogenesis, after treatment with cobalt chloride (CoCl2). Glucose uptake by luteal cells increased 2.7 folds (P < 0.05) in response to insulin; a phenomenon related to increased expression of glucose transporter (GLUT) 4 and phosphorylation of protein kinase B (AKT). The gene expression of insulin receptor and SLC2A4 (codifier of GLUT4) genes after insulin stimulation increased on day 20 post ovulation (p.o.) and declined on day 40 p.o. (P < 0.05). Regarding potentially involved molecular mechanisms, the nuclear factor kappa B gene RELA was upregulated on days 30/40 p.o., when SLC2A4 mRNA was low, and the interleukin 6 (IL6) gene was upregulated in the first half of dioestrus, when SLC2A4 mRNA was high. CoCl2in luteal cell cultures increased the hypoxia-inducible factor HIF1A/HIF1A and the SLC2A4/GLUT4 expression, and decreased progesterone (P4) production and hydroxyl-delta-5-steroid dehydrogenase 3 beta (HSD3B) mRNA expression (P < 0.05). This study shows that the canine luteal cells are responsive to insulin, which stimulates glucose uptake in AKT/GLUT4-mediated pathway; that may be related to local activity of RELA and IL6. Besides, the study reveals that luteal cells under hypoxia activate HIF1A-modulating luteal function and insulin-stimulated glucose uptake. These data indicate that insulin regulates luteal cells' glucose disposal, participating in the maintenance and functionality of the corpus luteum.
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Liza Margareth Medeiros de Carvalho
LM
Sousa
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Renata Dos Santos
RD
Silva
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Vanessa Uemura da
VU
Fonseca
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Rafael Magdanelo
RM
Leandro
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Thiago Senna
TS
Di Vincenzo
Department of Physiology and BiophysicsInstitute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Ana Bárbara
AB
Alves-Wagner
Department of Physiology and BiophysicsInstitute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Ubiratan Fabres
UF
Machado
Department of SurgerySchool of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil ppapa@usp.br.
Paula de Carvalho
PC
Papa
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism*; D003340:Corpus Luteum Maintenance / Q000235:genetics / Q000378:metabolism; D004285:Dogs / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D015850:Interleukin-6; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D003035:Cobalt; D011972:Receptor, Insulin; C018021:cobaltous chloride; D005947:Glucose
RELA/p65; corpus luteum; glucose uptake; hypoxia; insulin