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Altered function and expression of the orphan GPR135 at the cardiovascular level in diabetic Wistar rats
Armando Ruiz-Hernández1, Rodrigo Romero-Nava2, Fengyang Huang2
1a Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional , Ciudad de México , México.
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.
Insights
This study investigated the orphan receptor GPR135 in diabetic rats, finding it expressed in multiple tissues and altered by diabetes. GPR135 appears functional and may contribute to diabetic cardiovascular complications.
Area of Science:
- Endocrinology
- Cardiovascular Research
- Molecular Biology
Background:
- Cardiovascular complications are a leading cause of mortality in diabetes.
- Changes in G protein-coupled receptors (GPCRs), including orphan receptors, are linked to diabetic complications.
- The role of the orphan receptor GPR135 in diabetes remains largely unknown.
Purpose of the Study:
- To investigate the expression of the orphan receptor GPR135 in various tissues of diabetic rats.
- To determine the functional role of GPR135 in the context of diabetes and its potential link to cardiovascular complications.
Main Methods:
- Studied GPR135 expression in brain, heart, kidney, aorta, lung, spleen, and liver of diabetic rats.
- Utilized small interfering RNA (siRNA) to modulate GPR135 function.
- Administered isoproterenol to assess functional responses.
Main Results:
- GPR135 is expressed in all analyzed tissues.
- Diabetes significantly modifies GPR135 expression.
- siRNA-mediated GPR135 inhibition increased responses to isoproterenol in diabetic rats.
Conclusions:
- The orphan receptor GPR135 is expressed across multiple tissues and its expression is altered in diabetes.
- GPR135 is functional and appears coupled to Gi/o proteins, mediating negative chronotropic and inotropic effects.
- GPR135 may play a role in the cardiovascular complications associated with diabetes.
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