Carotid body denervation improves hyperglycemia in obese mice

Authors

Mi-Kyung Shin, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States.
Wan-Yee Tang, Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania, United States.
Mateus R. Amorim, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States.
James S-K Sham, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.
Vsevolod Y. Polotsky, Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States.

Document Type

Journal Article

Publication Date

2-1-2024

Journal

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

Volume

136

Issue

2

DOI

10.1152/japplphysiol.00215.2023

Keywords

Trpm7; carotid body; glucose metabolism; leptin; obese

Abstract

The carotid bodies (CBs) have been implicated in glucose abnormalities in obesity via elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) signaling and by 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 knockdown of , and gene expression in CB. In series of experiments in 75 male diet-induced obese (DIO) mice, we performed either CSND (vs. sham) surgeries or shRNA-induced suppression of , , or gene 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 (FFAs) levels, hepatic 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 . This paper provides first evidence that carotid body denervation abolishes hypertension and improves fasting blood glucose levels and glucose tolerance in mice with diet-induced obesity. Furthermore, we have shown that this phenomenon is associated with increased liver glycogen content, whereas insulin sensitivity and enzymes of gluconeogenesis were not affected.

APA Citation

Shin, Mi-Kyung; Tang, Wan-Yee; Amorim, Mateus R.; Sham, James S-K; and Polotsky, Vsevolod Y., "Carotid body denervation improves hyperglycemia in obese mice" (2024). GW Authored Works. Paper 4434.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4434

Department

Pharmacology and Physiology