TY - JOUR

T1 - Acute hypoglycemia in healthy humans impairs insulin stimulated glucose uptake and glycogen synthase in skeletal muscle

T2 - A randomized clinical study

AU - Voss, Thomas S

AU - Vendelbo, Mikkel H

AU - Kampmann, Ulla

AU - Hingst, Janne Rasmuss

AU - Wojtaszewski, Jørgen

AU - Svart, Mads V

AU - Møller, Niels

AU - Jessen, Niels

N1 - CURIS 2017 NEXS 229

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.2337/db16-1559

DO - 10.2337/db16-1559

M3 - Journal article

C2 - 28596236

VL - 66

SP - 2483

EP - 2494

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -