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

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 - 2017/9

Y1 - 2017/9

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. Our study used a crossover design to test to what extent insulin-induced hypoglycemia affects glucose uptake in skeletal muscle and whether hypoglycemia counterregulation modulates insulin and catecholamine signaling and glycogen synthase activity in skeletal muscle. Nine healthy volunteers were examined on three randomized study days: 1) hyperinsulinemic hypoglycemia (bolus insulin), 2) hyperinsulinemic euglycemia (bolus insulin and glucose infusion), and 3) saline control with skeletal muscle biopsies taken just before, 30 min after, and 75 min after insulin/saline injection. During hypoglycemia, glucose levels reached a nadir of ∼2.0 mmol/L, and epinephrine rose to ∼900 pg/mL. Hypoglycemia impaired insulin-stimulated glucose disposal and glucose clearance in skeletal muscle, whereas insulin signaling in glucose transport was unaffected by hypoglycemia. Insulin-stimulated glycogen synthase activity was completely ablated during hyperinsulinemic hypoglycemia, and catecholamine signaling via cAMP-dependent protein kinase and 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. Our study used a crossover design to test to what extent insulin-induced hypoglycemia affects glucose uptake in skeletal muscle and whether hypoglycemia counterregulation modulates insulin and catecholamine signaling and glycogen synthase activity in skeletal muscle. Nine healthy volunteers were examined on three randomized study days: 1) hyperinsulinemic hypoglycemia (bolus insulin), 2) hyperinsulinemic euglycemia (bolus insulin and glucose infusion), and 3) saline control with skeletal muscle biopsies taken just before, 30 min after, and 75 min after insulin/saline injection. During hypoglycemia, glucose levels reached a nadir of ∼2.0 mmol/L, and epinephrine rose to ∼900 pg/mL. Hypoglycemia impaired insulin-stimulated glucose disposal and glucose clearance in skeletal muscle, whereas insulin signaling in glucose transport was unaffected by hypoglycemia. Insulin-stimulated glycogen synthase activity was completely ablated during hyperinsulinemic hypoglycemia, and catecholamine signaling via cAMP-dependent protein kinase and 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

SN - 0012-1797

VL - 66

SP - 2483

EP - 2494

JO - Diabetes

JF - Diabetes

IS - 9

ER -