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

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.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Xu X,Liu B,Yang J,Zou Y,Sun M,Li Z,Li L,Yang R,Zou L,Li G,Liu S,Li G,Liang S

doi

10.1016/j.brainresbull.2020.10.004

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

290-297

eissn

0361-9230

issn

1873-2747

pii

S0361-9230(20)30661-4

journal_volume

165

pub_type

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