Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade
| Autor: | Niels Jessen, Mads Svart, Hans Stødkilde-Jørgensen, Niels Møller, Jens Otto Lunde Jørgensen, Janne Lebeck, Morten Hogild Pedersen, Martin Bidlingmaier, Steen B. Pedersen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Blood Glucose Male 0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Adipose tissue 030209 endocrinology & metabolism Context (language use) Carbohydrate metabolism Biochemistry Placebos Young Adult 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Lipid oxidation Internal medicine Journal Article medicine Humans Insulin Obesity Cross-Over Studies Human Growth Hormone business.industry Biochemistry (medical) Fasting Glucose clamp technique Lipid Metabolism medicine.disease Glucose 030104 developmental biology Adipose Tissue Glucose Clamp Technique Insulin Resistance business Hormone |
| Zdroj: | Pedersen, M H, Svart, M V, Lebeck, J, Bidlingmaier, M, Stødkilde-Jørgensen, H, Pedersen, S B, Møller, N, Jessen, N & Jørgensen, J O L 2017, ' Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade ', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 4, pp. 1340-1349 . https://doi.org/10.1210/jc.2016-3835 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2016-3835 |
| Popis: | Context: Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. Objective: To study the metabolic effects of GH blockade during fasting in obese subjects. Subjects and Methods: Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. Results: GH levels increased with fasting (P < 0.01), and the fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P < 0.05). Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P, 0.01) primarily due to reduced endogenous glucose production (P = 0.003). Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Conclusions: Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. |
| Databáze: | OpenAIRE |
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