Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content during hypoglycaemia in type 1 diabetic subjects.
In healthy subjects, hypoglycaemia induces a profound 80% reduction in skeletal muscle glucose uptake and a similar suppression of glycogen synthase activity. The aim of this study was to examine the efficacy of this counterregulatory mechanism in type 1 diabetic subjects, who are especially prone to hypoglycaemic incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min of hyperinsulinaemic (1.5 mU x kg(-1) x min(-1)) euglycaemia followed by (i) 240 min of graded hypoglycaemia (glucose nadir 2.8 mM) or (ii) 240 min of euglycaemia. At 345-360 min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 320-340 min. The sensitivity of glycogen synthase to glucose-6-P was reduced by hypoglycaemia, as shown by an increase in A0.5 for glucose-6-P (at 0.07 mmol/L) from 0.21+/-0.02 to 0.28+/-0.03 mM (p=0.06). Likewise, the fractional velocity for glycogen synthase was reduced by 25%; i.e. from 20.8+/-2.0 to 15.5+/-1.4% (p<0.05). Total glucose disposal was decreased during hypoglycaemia (5.3+/-0.6 vs. 8.3+/-0.7 mg x kg(-1) x min(-1) (euglycaemia), n = 9; p<0.05), primarily due to a reduction of non-oxidative glucose disposal (2.7+/-0.3 vs. 5.1+/-0.6 mg x kg(-1) x min(-1) (euglycaemia), n=7; p<0.05). Forearm arteriovenous glucose differences were decreased by 50% in the hypoglycaemic situation (0.7+/-0.1 vs. 1.4+/-0.3 mmol/L (320-340 min)), and counterregulatory hormonal responses seemed less conspicuous than described in healthy subjects. We conclude that hypoglycaemia induces decrements of forearm glucose uptake and glycogen synthase activity in type 1 diabetic subjects. The study indicates a decreased magnitude of these responses, but this remains to be confirmed.
Orskov
L
L
Department of Medicine C, Aarhus University Hospital, Denmark. L.Oerskov@dadlnet.dk
Schmitz
O
O
Bak
J F
JF
Lund
S
S
Kaal
A
A
Nyholm
B
B
Møller
N
N
D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004837:Epinephrine / Q000097:blood; D005542:Forearm; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D051275:Glucose Transporter Type 4; D006006:Glycogen Synthase / Q000378:metabolism*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D008055:Lipids; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D019382:Human Growth Hormone; D005934:Glucagon; D006006:Glycogen Synthase; D005947:Glucose; D006854:Hydrocortisone; D004837:Epinephrine