title: Factors affecting the activation of glycogen synthase in primary culture cardiomyocytes.
abstract: The ability of insulin, IGF-1 and IGF-2 to stimulate the activation of glycogen synthase in the heart was compared under completely defined conditions using primary culture cardiomyocytes. Both insulin and IGF-1 produced similar time- and concentration-dependent activation of glycogen synthase with the maximum stimulation observed at 10-15 min following hormone administration and at > or = 10 nM insulin or IGF-1. IGF-2 was largely ineffective at physiological concentrations. When primary culture cardiomyocytes were incubated with 100 microM palmitate for 2 h and then challenged with various concentrations of insulin or IGF-1, there was a significant decrease in the ability of the cells to activate glycogen synthase. In addition, maintaining cardiomyocytes in hormone deficient culture conditions for 24 or 48 h also resulted in a reduced ability to activate glycogen synthase in response to these hormones. These results suggest that (1) both insulin and IGF-1 are potent regulators of glycogen synthesis in the heart, (2) the enzymes involved in the dephosphorylation (activation) of glycogen synthase are closely linked to both insulin and IGF-1, but not IGF-2 receptor signaling pathways, (3) glycogen synthase activation is adversely affected by the maintenance of cardiomyocytes in the presence of palmitate or for > or = 24 h in hormone deficient media which results in insulin and IGF-1 resistance, and (4) this resistance, like that found in cells from diabetic rats, is due at least in part to a decrease in glycogen synthase phosphatase activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: S R
authors.initials: SR
authors.lastname: Jaspers
authors.forename: A K
authors.initials: AK
authors.lastname: Garnache
authors.forename: T B
authors.initials: TB
authors.lastname: Miller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004789:Enzyme Activation; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D006006:Glycogen Synthase