Related Experiment Video
Updated: Jul 17, 2026
High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized
Melanie G Cree1, Jennifer J Zwetsloot, David N Herndon
1Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555, USA. mecree@utmb.edu
Insights
Fenofibrate treatment improved insulin sensitivity and reduced glucose levels in children with severe burns. This PPAR-alpha agonist shows promise for treating post-burn insulin resistance.
Area of Science:
- Metabolic research
- Trauma care
- Pharmacology
Background:
- Hyperglycemia is common after severe burns but the mechanisms of insulin resistance are poorly understood.
- Limited therapeutic options exist for managing post-burn hyperglycemia and insulin resistance.
Purpose of the Study:
- To investigate the mechanisms of insulin resistance after burn trauma.
- To evaluate the effectiveness of PPAR-alpha agonism (fenofibrate) in improving insulin resistance in pediatric burn patients.
Main Methods:
- A double-blind, placebo-controlled trial involving 21 children (4-16 years) with extensive burns (>40% TBSA).
- Treatment with fenofibrate or placebo for 2 weeks within 3 weeks of injury.
- Assessment of whole-body and hepatic insulin sensitivity using hyperinsulinemic-euglycemic clamp.
- Analysis of muscle biopsies for insulin signaling and mitochondrial function.
Main Results:
- Fenofibrate significantly reduced daily glucose concentrations compared to placebo (P=0.004).
- Insulin-stimulated glucose uptake increased significantly with fenofibrate treatment (P=0.003).
- Fenofibrate enhanced insulin signaling (receptor and IRS-1 phosphorylation) and improved mitochondrial ATP production (P=0.001).
Conclusions:
- Early fenofibrate treatment (within 1 week postburn) for 2 weeks improved insulin sensitivity, signaling, and mitochondrial glucose oxidation.
- Fenofibrate demonstrates potential as a novel therapeutic agent for managing insulin resistance in severe burn injuries.
Objective:
To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to determine the efficacy of PPAR-alpha agonism for alleviating insulin resistance in this population.
Summary Background Data:
Hyperglycemia following trauma, especially burns, is well documented. However, the underlying insulin resistance is not well understood, and there are limited treatment options.
Methods:
Twenty-one children 4 to 16 years of age with >40% total body surface area burns were enrolled in a double-blind, prospective, placebo-controlled randomized trial. Whole body and liver insulin sensitivity were assessed with a hyperinsulinemic-euglycemic clamp, and insulin signaling and mitochondrial function were measured in muscle biopsies taken before and after approximately 2 weeks of either placebo (PLA) or 5 mg/kg of PPAR-alpha agonist fenofibrate (FEN) treatment, within 3 weeks of injury.
Results:
The change in average daily glucose concentrations was significant between groups after treatment (146 +/- 9 vs. 161 +/- 9 mg/dL PLA and 158 +/- 7 vs. 145 +/- 4 FEN; pretreatment vs. posttreatment; P = 0.004). Insulin-stimulated glucose uptake increased significantly in FEN (4.3 +/- 0.6 vs. 4.5 +/- 0.7 PLA and 5.2 +/- 0.5 vs. 7.6 +/- 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003). Insulin trended to suppress hepatic glucose release following fenofibrate treatment (P = 0.06). Maximal mitochondrial ATP production from pyruvate increased significantly after fenofibrate (P = 0.001) and was accompanied by maintained levels of cytochrome C oxidase and citrate synthase activity levels. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 in response to insulin increased significantly following fenofibrate treatment (P = 0.04 for both).
Conclusions:
Fenofibrate treatment started within 1 week postburn and continued for 2 weeks significantly decreased plasma glucose concentrations by improving insulin sensitivity, insulin signaling, and mitochondrial glucose oxidation. Fenofibrate may be a potential new therapeutic option for treating insulin resistance following severe burn injury.
