Is the canine corpus luteum an insulin-sensitive tissue?

Author(s)

Medeiros de Carvalho Sousa, Liza Margareth ; Silva, Renata dos Santos ; da Fonseca, Vanessa Uemura ; Leandro, Rafael Magdanelo ; di Vincenzo, Thiago Senna ; Alves-Wagner, Ana Barbara ; Machado, Ubiratan Fabres ; Papa, Paula de Carvalho

• Document type: Journal article
• Source: Journal of Endocrinology; v. 231, n. 3, p. 223-233, DEC 2016.
• Web of Science Citations: 0

Abstract

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. CoCl2 in 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. (AU)

• FAPESP's process: 11/17768-3 - 17b-estradiol role on the luteolytic process in non-pregnant dogs
• Grantee: Paula de Carvalho Papa Keohane
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/07373-9 - Corpus luteum and diestrus in the bitch: a study model for hormonal-dependent metabolic alterations
• Grantee: Paula de Carvalho Papa Keohane
• Support Opportunities: Scholarships abroad - Research