Experimental physiology | 2021
Hyperpolarized [1-13 C]pyruvate combined with the hyperinsulinemic euglycemic and hypoglycemic clamp technique in skeletal muscle in a large animal model.
Abstract
NEW FINDINGS\nWhat is the central question of this study? Is it possible to combine the hyperpolarized magnetic resonance technique and the hyperinsulinemic clamp method in order to evaluate skeletal muscle metabolism in a large animal model. What is the main finding and its importance? The logistical setup is possible, and we found substantial increments in glucose infusion rates representing skeletal muscle glucose uptake yet no differences in ratios of [1-13 C]lactate to [1-13 C]pyruvate, [1-13 C]alanine to [1-13 C]pyruvate, and 13 C-bicarbonate to [1-13 C]pyruvate implying that the hyperpolarization technique may not be optimal for detecting insulin effects in anesthetized skeletal muscle, which is of significant knowledge in future studies.\n\n\nABSTRACT\nBackground and aim : In skeletal muscle, glucose metabolism is tightly regulated by the reciprocal relationship between insulin and adrenaline with pyruvate being at the intersection of both pathways. Hyperpolarized magnetic resonance (hMR) is a novel approach to gain insights into these pathways, and human trials involving hMR and skeletal muscle metabolism are imminent. We aimed to combine the hyperinsulinemic clamp technique and hMR in a large animal model resembling human physiology.\n\n\nMATERIALS AND METHODS\nFifteen anaesthetized pigs were randomized to saline (control group), hyperinsulinemic euglycemic clamp technique (HE group) or hyperinsulinemic hypoglycemic clamp technique (HH group). Skeletal muscle metabolism was evaluated by hyperpolarized [1-13 C]pyruvate injection and hMR at baseline and after intervention.\n\n\nRESULTS\nGlucose infusion rate per kilogram increased by a statistically significant amount in the HE and HH groups (p<0.001). hMR showed no statistically significant metabolite ratio changes; [1-13 C]lactate to [1-13 C]pyruvate in the HH group vs. control group (p = 0.19), and 13 C-bicarbonate to [1-13 C]pyruvate ratio in the HE group vs. the control group (p = 0.12).\n\n\nCONCLUSION\nWe found evidence of profound increments in glucose infusion rates representing skeletal muscle glucose uptake, but interestingly, no signs of significant changes in aerobic and anaerobic metabolism using hMR. These results imply that hyperpolarized [1-13 C]pyruvate may not be optimally suited to detect insulin effects in anaesthetized resting skeletal muscle, which is of significant knowledge in future studies. This article is protected by copyright. All rights reserved.