Glucokinase in stellate ganglia cooperates with P2X3 receptor to develop cardiac sympathetic neuropathy in type 2 diabetes rats

Brain Res Bull. 2020 Dec:165:290-297. doi: 10.1016/j.brainresbull.2020.10.004. Epub 2020 Oct 20.

Abstract

Glucokinase (GCK) may be involved in inflammatory pathological changes, while the P2X3 receptor in the stellate ganglia (SG) is related to diabetic cardiac autonomic neuropathy. In this study, we explored the relationship between the upregulated GCK in SG and diabetic cardiac sympathy. The expression and location of GCK and P2X3 in SG of type 2 diabetes mellitus (T2DM) rats were assessed. Changes in cardiac function were determined by measuring blood pressure, sympathetic nerve activity, heart rate, and heart rate variability. P2X3 agonist-activated currents in isolated stellate ganglion neurons and cultured human embryonic kidney 293 (HEK293) cells were recorded using whole-cell patch clamp techniques. The upregulated expression of GCK in SG of T2DM rats was decreased after treatment with GCK short hairpin RNA (shRNA). GCK shRNA treatment also improved the blood pressure, sympathetic nerve activity, heart rate, and heart rate variability in T2DM rats. By contrast, the expression of P2X3 and tumor necrosis factor α (TNF-α) was lessened by GCK shRNA treatment. In addition, adenosine triphosphate (ATP)-activated currents in stellate ganglion neurons and HEK293 cells co-transfected with GCK and P2X3 receptor plasmids were reduced after GCK shRNA treatment. In T2DM rats, knockdown of GCK relieved the diabetic cardiac sympathy mediated by P2X3 receptor-involved upregulation of GCK in SG.

Keywords: Diabetic cardiac sympathy; Glucokinase; P2X3 receptor; Stellate ganglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / physiopathology
  • Glucokinase / metabolism*
  • HEK293 Cells
  • Heart Rate / physiology
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X3 / metabolism*
  • Stellate Ganglion / metabolism*
  • Stellate Ganglion / physiopathology
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology

Substances

  • Receptors, Purinergic P2X3
  • Glucokinase