Acute hypoglycemia in healthy humans impairs insulin stimulated glucose uptake and glycogen synthase in skeletal muscle: A randomized clinical study
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Hypoglycemia is the leading limiting factor in glycemic management of insulin-treated diabetes. Skeletal muscle is the predominant site of insulin-mediated glucose disposal and our study was designed to test to what extent insulin induced hypoglycemia affects glucose uptake in skeletal muscle and whether hypoglycemia counter-regulation modulates insulin and catecholamine signaling and glycogen synthase activity in skeletal muscle.Nine healthy volunteers were examined on three randomized study days in a crossover design: i) hyperinsulinemic hypoglycemia (bolus insulin), ii) hyperinsulinemic euglycemia (bolus insulin and glucose infusion) and iii) saline control with skeletal muscle biopsies taken just before, 30 min and 75 min after insulin/saline injection.During hypoglycemia glucose levels reached a nadir of ∼2.0mmol/l and epinephrine rose to ∼900pg/ml.Insulin stimulated glucose disposal and glucose clearance in skeletal muscle were impaired whereas insulin signaling to glucose transport was unaffected by hypoglycemia. Insulin-stimulated glycogen synthase activity was completely ablated during hyperinsulinemic hypoglycemia and catecholamine signaling via PKA as well as phosphorylation of inhibiting sites on glycogen synthase all increased.
Original language | English |
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Journal | Diabetes |
Volume | 66 |
Issue number | 9 |
Pages (from-to) | 2483-2494 |
Number of pages | 12 |
ISSN | 0012-1797 |
DOIs | |
Publication status | Published - 2017 |
- Journal Article
Research areas
ID: 179366280