Acute hypoglycemia in healthy humans impairs insulin stimulated glucose uptake and glycogen synthase in skeletal muscle: A randomized clinical study

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind66
Udgave nummer9
Sider (fra-til)2483-2494
Antal sider12
ISSN0012-1797
DOI
StatusUdgivet - 2017

Bibliografisk note

CURIS 2017 NEXS 229

ID: 179366280