Glycogen Synthase Activity in Adipose Tissue

2003 ◽  
pp. 089-096
Author(s):  
Heidi K. Ortmeyer
Keyword(s):  
Adipose Tissue ◽  
Glycogen Synthase ◽  
Glycogen Synthase Activity

Fasting and diabetes alter adipose tissue glycogen synthase

1984 ◽  
Vol 247 (5) ◽  
pp. E581-E584
Author(s):  
H. R. Kaslow ◽  
R. D. Eichner
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Enzyme Purification ◽  
Glycogen Synthase ◽  
Streptozotocin Diabetes ◽  
Positive Cooperativity ◽  
Maximal Activation ◽  
Glucose Incorporation ◽  
Glycogen Synthase Activity

In a previous report (J. Biol. Chem. 254: 4678-4683, 1979), we showed that fasting blunted the ability of insulin to promote glucose incorporation into glycogen in vitro. In addition, we showed that glycogen synthase activity was altered in two ways: the concentration of glucose 6-P causing half-maximal activation increased, and positive cooperativity appeared in the glucose 6-P activation of the enzyme. We now show that streptozotocin-diabetes causes the same changes in glucose incorporation and glycogen synthase activity. We show that these changes in glycogen synthase activity persist during enzyme purification; thus it is likely the changes are a result of a structural alteration of the enzyme. Because glycogenolysis of a glycogen particle from rabbit skeletal muscle also caused the appearance of positive cooperativity, we propose that both phosphorylation and glycogenolysis are involved in the appearance of positive cooperativity.

Fat feeding impairs glycogen synthase activity in mice without effects on its gene expression

Metabolism ◽  
2003 ◽  
Vol 52 (5) ◽  
pp. 535-539 ◽  
Author(s):  
Xudong Huang ◽  
Mona Hansson ◽  
Esa Laurila ◽  
Bo Ahrén ◽  
Leif Groop
Keyword(s):  
Gene Expression ◽  
Glycogen Synthase ◽  
Its Gene ◽  
Fat Feeding ◽  
Glycogen Synthase Activity

Pharmacological characterization of a small molecule inhibitor of c-Jun kinase

2008 ◽  
Vol 295 (5) ◽  
pp. E1142-E1151 ◽  
Author(s):  
Helen Cho ◽  
Shawn C. Black ◽  
David Looper ◽  
Manli Shi ◽  
Dawn Kelly-Sullivan ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Body Fat ◽  
Small Molecule ◽  
Glycogen Synthase ◽  
High Fat ◽  
Pharmacological Characterization ◽  
Compound A ◽  
Weight Decrease

c-Jun NH2-terminal kinase (JNK) plays an important role in insulin resistance; however, identification of pharmacologically potent and selective small molecule JNK inhibitors has been limited. Compound A has a cell IC50 of 102 nM and is at least 100-fold selective against related kinases and 27-fold selective against glycogen synthase kinase-3β and cyclin-dependent kinase-2. In C57BL/6 mice, compound A reduced LPS-mediated increases in both plasma cytokine levels and phosphorylated c-Jun in adipose tissue. Treatment of mice fed a high-fat diet with compound A for 3 wk resulted in a 13.1 ± 1% decrease in body weight and a 9.3 ± 1.5% decrease in body fat, compared with a 6.6 ± 2.1% increase in body weight and a 6.7 ± 2.1% increase in body fat in vehicle-treated mice. Mice pair fed to those that received compound A exhibited a body weight decrease of 7 ± 1% and a decrease in body fat of 1.6 ± 1.3%, suggesting that reductions in food intake could not account solely for the reductions in adiposity observed. Compound A dosed at 30 mg/kg for 13 days in high-fat fed mice resulted in a significant decrease in phosphorylated c-Jun in adipose tissue accompanied by a decrease in weight and reductions in glucose and triglycerides and increases in insulin sensitivity to levels comparable with those in lean control mice. The ability of compound A to reduce the insulin-stimulated phosphorylation of insulin receptor substrate-1 (IRS-1) von Ser307 and partially reverse the free fatty acid inhibition of glucose uptake in 3T3L1 adipocytes, suggests that enhancement of insulin signaling in addition to weight loss may contribute to the effects of compound A on insulin sensitization in vivo. Pharmacological inhibition of JNK using compound A may therefore offer an effective therapy for type 2 diabetes mediated at least in part via weight reduction.

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