CAROTID BODY DENERVATION IMPROVES HYPERGLYCEMIA IN OBESE MICE

Document Type

Journal Article

Publication Date

12-21-2023

Journal

Journal of applied physiology (Bethesda, Md. : 1985)

DOI

10.1152/japplphysiol.00215.2023

Keywords

Trpm7; carotid body; glucose metabolism; leptin; obese

Abstract

The carotid bodies (CB) have been implicated in glucose abnormalities in obesity elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) activation in CB, and may also be by high levels of circulating leptin, which binds to the leptin receptor (LEPR) in CB and activates transient receptor potential channel subfamily M member 7 (TRPM7). We hypothesize that in mice with diet-induced obesity, hyperglycemia, glucose intolerance and insulin resistance will be attenuated by the CB denervation (carotid sinus nerve dissection, CSND) and by genetic knockdown of , and In series of experiments in 75 male DIO mice, we performed either CSND (vs sham) surgeries or shRNA-induced suppression of , or expression in CB, followed by blood pressure telemetry, intraperitoneal glucose tolerance and insulin tolerance tests, and measurements of fasting plasma insulin, leptin, corticosterone, glucagon and free fatty acids (FFA), liver expression of gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G-6-Pase) mRNA and liver glycogen levels. CSND decreased blood pressure, fasting blood glucose levels and improved glucose tolerance without any effect on insulin resistance. CSND did not affect any hormone levels and gluconeogenesis enzymes, but increased liver glycogen level. Genetic knockdown of CB , and had no effect on glucose metabolism. We conclude that CB contributes to hyperglycemia of obesity, probably by modulation of the glycogen-glucose equilibrium. Diabetogenic effects of obesity on CB in mice do not occur via activation of CB , and .

Department

Anesthesiology and Critical Care Medicine

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