Lipids and ketones dominate metabolism at the expense of glucose control in pulmonary arterial hypertension: a hyperglycaemic clamp and metabolomics study
| Autor: | Gustavo A. Heresi, Melissa L. Erickson, John P. Kirwan, Jacob T. Mey, Ciaran E. Fealy, Adithya Hari, Raed A. Dweik, Christopher L. Axelrod |
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| Přispěvatelé: | Nutrition and Movement Sciences, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health |
| Rok vydání: | 2020 |
| Předmět: |
Blood Glucose
0301 basic medicine Pulmonary and Respiratory Medicine medicine.medical_specialty CLEARANCE medicine.medical_treatment Fatty Acids Nonesterified 030204 cardiovascular system & hematology c-peptide Article resistance 03 medical and health sciences 0302 clinical medicine Metabolomics Lipid oxidation bodies HEPATIC EXTRACTION Internal medicine medicine Humans Insulin Familial Primary Pulmonary Hypertension chemistry.chemical_classification Pulmonary Arterial Hypertension obese beta-cell function INSULIN SENSITIVITY business.industry Skeletal muscle Fatty acid Metabolism Ketones secretion Glucose 030104 developmental biology Clamp medicine.anatomical_structure Endocrinology chemistry Hyperglycemia ACID Ketone bodies Insulin Resistance business |
| Zdroj: | Eur Respir J European Respiratory Journal, 55(4):1901700. European Respiratory Society |
| ISSN: | 1399-3003 0903-1936 |
| DOI: | 10.1183/13993003.01700-2019 |
| Popis: | Individuals with idiopathic pulmonary arterial hypertension (PAH) display reduced oral glucose tolerance. This may involve defects in pancreatic function or insulin sensitivity but this hypothesis has not been tested; moreover, fasting nutrient metabolism remains poorly described in PAH. Thus, we aimed to characterise fasting nutrient metabolism and investigated the metabolic response to hyperglycaemia in PAH.12 participants (six PAH, six controls) were administered a hyperglycaemic clamp, while 52 (21 PAH, 31 controls) underwent plasma metabolomic analysis. Glucose, insulin, C-peptide, free fatty acids and acylcarnitines were assessed from the clamp. Plasma metabolomics was conducted on fasting plasma samples.The clamp verified a reduced insulin response to hyperglycaemia in PAH (−53%versuscontrol), but with similar pancreatic insulin secretion. Skeletal muscle insulin sensitivity was unexpectedly greater in PAH. Hepatic insulin extraction was elevated in PAH (+11%versuscontrol). Plasma metabolomics identified 862 metabolites: 213 elevated, 145 reduced in PAH (pPoor glucose control in PAH could not be explained by pancreatic β-cell function or skeletal muscle insulin sensitivity. Instead, elevated hepatic insulin extraction emerged as an underlying factor. In agreement, nutrient metabolism in PAH favours lipid and ketone metabolism at the expense of glucose control. Future research should investigate the therapeutic potential of reinforcing lipid and ketone metabolism on clinical outcomes in PAH. |
| Databáze: | OpenAIRE |
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