Resistin impairs basal and insulin-induced glycogen synthesis by different mechanisms.
In the present study, we investigated the mechanisms by which resistin (100 nM, 1 h) affects glycogen synthesis in L6 skeletal muscle cells. The activity of glycogen synthase, the major enzyme in glycogen synthesis, is determined by both its covalent phosphorylation and allostery through intracellular glucose-6-phosphate. Covalent phosphorylation of glycogen synthase was not altered by resistin and, accordingly, phosphorylation of GSK-3alpha/beta and Akt remained unchanged. The rate of glucose-6-phosphate formation, however, was decreased by resistin both in the absence and presence of insulin; in the absence of insulin, resistin decreased glucose-6-phosphate formation by reducing hexokinase type I activity without affecting glucose uptake; by contrast, in the presence of insulin, resistin decreased glucose-6-phosphate formation by reducing the Vmax of glucose uptake without changing hexokinase type I activity. In conclusion, short-term resistin incubation impairs glycogen synthesis by reducing the rate of glucose-6-phosphate formation involving, however, differential mechanisms in basal and insulin-stimulated states.
Niederwanger
Andreas
A
Clinical Department of Internal Medicine, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Kranebitter
Michael
M
Ciardi
Christian
C
Tatarczyk
Tobias
T
Patsch
Josef R
JR
Pedrini
Michael T
MT
D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006593:Hexokinase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D052243:Resistin / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D052243:Resistin; D019298:Glucose-6-Phosphate; D006003:Glycogen; D006006:Glycogen Synthase; D006593:Hexokinase; D016315:Proto-Oncogene Proteins c-abl; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D005947:Glucose