Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine

Cotero, Victoria, Graf, John, Miwa, Hiromi, Hirschstein, Zall, Qanud, Khaled, Huerta, Tomás S, Tai, Ningwen, Ding, Yuyan, Jimenez-Cowell, Kevin, Tomaio, Jacquelyn N, Song, Weiguo, Devarajan, Alex, Tsaava, Tea, Madhavan, Radhika, Wallace, Kirk, Loghin, Evelina, Morton, Christine, Fan, Ying, Kao, Tzu-Jen, Akhtar, Kainat, Damaraju, Meghana, Barenboim, Linda, Maietta, Teresa, Ashe, Jeffrey, Tracey, Kevin J, Coleman, Thomas R, Di Carlo, Dino, Shin, Damian, Zanos, Stavros, Chavan, Sangeeta S, Herzog, Raimund I, Puleo, Chris (March 2022) Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine. Nature Biomedical Engineering. ISSN 2157-846X

Abstract

Peripheral neurons that sense glucose relay signals of glucose availability to integrative clusters of neurons in the brain. However, the roles of such signalling pathways in the maintenance of glucose homoeostasis and their contribution to disease are unknown. Here we show that the selective activation of the nerve plexus of the hepatic portal system via peripheral focused ultrasound stimulation (pFUS) improves glucose homoeostasis in mice and rats with insulin-resistant diabetes and in swine subject to hyperinsulinemic-euglycaemic clamps. pFUS modulated the activity of sensory projections to the hypothalamus, altered the concentrations of metabolism-regulating neurotransmitters, and enhanced glucose tolerance and utilization in the three species, whereas physical transection or chemical blocking of the liver-brain nerve pathway abolished the effect of pFUS on glucose tolerance. Longitudinal multi-omic profiling of metabolic tissues from the treated animals confirmed pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney and intestinal tissues. Non-invasive ultrasound activation of afferent autonomic nerves may represent a non-pharmacologic therapy for the restoration of glucose homoeostasis in type-2 diabetes and other metabolic diseases.

Item Type:	Paper
Subjects:	diseases & disorders diseases & disorders > nutritional and metabolic diseases organism description > animal diseases & disorders > nutritional and metabolic diseases > diabetes organs, tissues, organelles, cell types and functions > tissues types and functions > suprachiasmatic nucleus > hypothalamus organs, tissues, organelles, cell types and functions > tissues types and functions > hypothalamus organs, tissues, organelles, cell types and functions > organs types and functions > liver organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Tracey, Kevin
Communities:	CSHL labs > Tracey lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	31 March 2022
Date Deposited:	15 Apr 2022 13:20
Last Modified:	11 Jan 2024 19:30
PMCID:	PMC10127248
URI:	https://repository.cshl.edu/id/eprint/40585

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