Scoping review maps glucose effects of hepatic sympathetic denervation

A new scoping review in the Journal of Vascular and Interventional Radiology takes stock of the evidence on celiac and hepatic sympathetic denervation and glucose homeostasis, pulling together both human and animal studies to clarify what is known, and what still isn’t. Per the abstract provided, the authors reviewed studies indexed through December 2025 that reported glucose outcomes after sympathetic denervation targeting the celiac plexus, the celiac/superior mesenteric ganglia, or perivascular nerves along the common hepatic artery. Their stated goal was practical: map the evidence base and identify gaps that should shape future trials.

The review lands at a moment when interest in metabolic neuromodulation is broadening beyond blood pressure and renal denervation. The physiologic rationale has been building for years. Reviews of hepatic autonomic biology describe sympathetic signaling as an important regulator of hepatic glucose metabolism, with excess sympathetic activity linked to increased hepatic glucose production and worsening glycemic control. A 2026 JACC Asia review framed combined hepatic and renal denervation as a translational, hypothesis-generating strategy for cardiometabolic disease, but stressed that the field still lacks the randomized evidence needed to establish efficacy or durability. (pubmed.ncbi.nlm.nih.gov)

That tension, strong mechanistic rationale but thin clinical proof, appears to be the core story. Preclinical studies have shown signals that sympathetic denervation can improve glucose handling. In dogs, selective common hepatic artery denervation lessened glucose intolerance, and classic physiology work found that removing hepatic sympathetic input can disinhibit hepatic glucose uptake during hyperglycemia. More recently, a rodent study reported that removal of the celiac and superior mesenteric ganglia improved glucose tolerance, with authors pointing to reduced sympathetic effects on both hepatic glycogenolysis and pancreatic hormone regulation. (pubmed.ncbi.nlm.nih.gov)

Human evidence is starting to emerge, but it remains preliminary. A 2025 multicenter, open-label, single-arm study evaluated catheter-based endovascular denervation of the celiac and hepatic arteries in 30 patients with poorly controlled type 2 diabetes after enrollment of 37 across three centers. That study adds clinical momentum, but its design limits what can be concluded about causality, placebo effects, and durability. The 2026 JACC Asia review makes the same point explicitly, noting that available human studies are small, single-arm, and not sham-controlled. (pubmed.ncbi.nlm.nih.gov)

Older human denervation data also complicate the picture in useful ways. Liver transplantation creates a natural model of hepatic denervation. In a 1997 human study, transplant recipients generally maintained normal postabsorptive glucose metabolism and showed largely normal responses to glucose and insulin challenges, but they also had altered insulin and glucagon dynamics and a blunted counterregulatory response during hypoglycemia. Separate work found no evidence of sympathetic reinnervation during the first years after transplantation. Together, those findings suggest that denervation may not simply “improve glucose” in a straightforward way; it may reshape broader autonomic-metabolic circuits, including safety-critical responses to low blood glucose. (pubmed.ncbi.nlm.nih.gov)

There doesn’t appear to be substantial independent expert commentary tied specifically to this scoping review yet, but the surrounding literature is cautious. Recent reviews consistently describe hepatic denervation as investigational, translational-stage, and in need of rigorous trial design. That caution is reinforced by anatomy and device considerations discussed in the 2026 JACC Asia review, which notes that nerve depth distribution, proximity to adjacent structures, and possible nerve regeneration all complicate interpretation of early feasibility studies. (pubmed.ncbi.nlm.nih.gov)

Why it matters: For veterinary professionals, this is less about an immediately practice-changing intervention and more about where comparative metabolic research may be heading. The liver’s neural control of glucose homeostasis is relevant across species, and the review helps organize a fragmented literature that spans interventional radiology, endocrinology, physiology, and translational surgery. For clinicians and researchers working in obesity, diabetes, or large-animal models, the paper is a signal that autonomic-targeted therapies are moving from theory toward structured evaluation. At the same time, the liver transplant literature is a reminder that glycemic endpoints alone may miss clinically important consequences, especially around hypoglycemia awareness and counterregulation. (pubmed.ncbi.nlm.nih.gov)

What to watch: The next meaningful step is better human evidence: randomized, sham-controlled studies with longer follow-up, clearer target-engagement measures, and safety endpoints that include hypoglycemia physiology, not just HbA1c or glucose tolerance. If those data arrive, they’ll help determine whether hepatic or celiac sympathetic denervation remains an intriguing mechanistic idea, or becomes a credible metabolic intervention with translational relevance for veterinary and human medicine alike. (pubmed.ncbi.nlm.nih.gov)