Altered function and expression of the orphan GPR135 at the cardiovascular level in diabetic Wistar rats

Abstract

Cardiovascular complications are the main cause of mortality in patients with diabetes, these have been associated with changes in function and expression of receptors coupled to G proteins (GPCR), which include orphan receptors which some of them tend to modify in diabetes, although others are not known, such as GPR135. For this reason, the objective of this work was to study the expression of the orphan receptor GPR135 in brain, heart, kidney, aorta, lung, spleen and liver of diabetic rats, as well as its function by the administration of siRNA (small interfering RNA) and curves to isoproterenol. Our results showed that GPR135 is expressed in all tissues analyzed and its expression is modified due to diabetes, we also observed that the responses to isoproterenol increase in diabetic rats administered with siRNA. Therefore, we conclude that the orphan receptor GPR135 is expressed in different tissues and its expression tends to be modified due to diabetes, besides that it is functional and that it seems to be coupled to Gi/o protein which has negative chronotropic and inotropic effects, therefore, we do not rule out that it participates in the cardiovascular complications associated with diabetes.

Keywords:

• Cardiovascular complications
• GPR135
• orphan receptor
• siRNA

Acknowledgement

The authors would like thank to Dr. César Romel Barrientos Maldonado for his valuable participation in the elaboration of this work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants CONACYT CB-2012–01-183660 (Consejo Nacional de Ciencia y Tecnología), project SIP-IPN-20161519 (Secretaría de Investigación y Posgrado del Instituto Politécnico Nacional), and CONACYT Scholarship to the student Armando Ruiz Hernández.