scholarly journals Inhibition of Insulin-Stimulated Glycogen Synthesis by 5-Aminoimidasole-4-Carboxamide-1-β-d-Ribofuranoside-Induced Adenosine 5′-Monophosphate-Activated Protein Kinase Activation: Interactions with Akt, Glycogen Synthase Kinase 3-3α/β, and Glycogen Synthase in Isolated Rat Soleus Muscle

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5170-5177 ◽  
Author(s):  
S. Fediuc ◽  
M. P. Gaidhu ◽  
R. B. Ceddia

The aim of this study was to investigate the effects of 5-aminoimidasole-4-carboxamide-1-β-d-ribofuranoside (AICAR)-induced AMP-activated protein kinase activation on glycogen metabolism in soleus (slow twitch, oxidative) and epitrochlearis (fast twitch, glycolytic) skeletal muscles. Isolated soleus and epitrochlearis muscles were incubated in the absence or presence of insulin (100 nm), AICAR (2 mm), and AICAR plus insulin. In soleus muscles exposed to insulin, glycogen synthesis and glycogen content increased 6.4- and 1.3-fold, respectively. AICAR treatment significantly suppressed (∼60%) insulin-stimulated glycogen synthesis and completely prevented the increase in glycogen content induced by insulin. AICAR did not affect either basal or insulin-stimulated glucose uptake but significantly increased insulin-stimulated (∼20%) lactate production in soleus muscles. Interestingly, basal glucose uptake was significantly increased (∼1.4-fold) in the epitrochlearis muscle, even though neither basal nor insulin-stimulated rates of glycogen synthesis, glycogen content, and lactate production were affected by AICAR. We also report the novel evidence that AICAR markedly reduced insulin-induced Akt-Thr308 phosphorylation after 15 and 30 min exposure to insulin, which coincided with a marked reduction in glycogen synthase kinase 3 (GSK)-3α/β phosphorylation. Importantly, phosphorylation of glycogen synthase was increased by AICAR treatment 45 min after insulin stimulation. Our results indicate that AICAR-induced AMP-activated protein kinase activation caused a time-dependent reduction in Akt308 phosphorylation, activation of glycogen synthase kinase-3α/β, and the inactivation of glycogen synthase, which are compatible with the acute reduction in insulin-stimulated glycogen synthesis in oxidative but not glycolytic skeletal muscles.

2019 ◽  
Vol 87 (September) ◽  
pp. 2827-2837
Author(s):  
HEND ASHOUR, M.D.; ASMAA M. SHAMSELDEEN, M.D. ◽  
HEBA S. SHOUKRY, M.D.; LAILA A. RASHED, M.D. ◽  
MOHAMED M. EL-SEBAIE, M.D.; MOHAMED H. ELSAYED, M.Sc. ◽  
SHEREEN ABDELFATTAH, M.D.; SAFINAZ SALAH-ELDIN, M.D. ◽  
HANIA I. AMMAR, M.D.

2004 ◽  
Vol 96 (5) ◽  
pp. 1606-1612 ◽  
Author(s):  
Claude Lajoie ◽  
Angelino Calderone ◽  
François Trudeau ◽  
Nathalie Lavoie ◽  
Guy Massicotte ◽  
...  

Cardiac dysfunction is a severe secondary effect of Type 2 diabetes. Recruitment of the protein kinase B/glycogen synthase kinase-3 pathway represents an integral event in glucose homeostasis, albeit its regulation in the diabetic heart remains undefined. Thus the following study tested the hypothesis that the regulation of protein kinase B/glycogen synthase kinase-3 was altered in the myocardium of the Zucker diabetic fatty rat. Second, exercise has been shown to improve glucose homeostasis, and, in this regard, the effect of swimming training on the regulation of protein kinase B/glycogen synthase kinase-3 in the diabetic rat heart was examined. In the sedentary Zucker diabetic fatty rats, glucose levels were elevated, and cardiac glycogen content increased, compared with wild type. A 13-wk swimming regimen significantly reduced plasma glucose levels and cardiac glycogen content and partially normalized protein kinase B-serine473, protein kinase B-threonine308, and glycogen synthase kinase-3α phosphorylation in Zucker diabetic fatty rats. In conclusion, hyperglycemia and increased cardiac glycogen content in the Zucker diabetic fatty rats were associated with dysregulation of protein kinase B/glycogen synthase kinase-3 phosphorylation. These anomalies in the Zucker diabetic fatty rat were partially normalized with swimming. These data support the premise that exercise training may protect the heart against the deleterious consequences of diabetes.


2021 ◽  
Vol 22 (3) ◽  
pp. 1384
Author(s):  
Itziar Eseberri ◽  
Claire Laurens ◽  
Jonatan Miranda ◽  
Katie Louche ◽  
Arrate Lasa ◽  
...  

Phenolic compounds have emerged in recent years as an option to face insulin resistance and diabetes. The central aim of this study was: (1) to demonstrate that physiological doses of resveratrol (RSV) or quercetin (Q) can influence glucose metabolism in human myotubes, (2) to establish whether AMP-activated protein kinase (AMPK) and protein kinase B –PKB- (Akt) pathways are involved in this effect. In addition, the effects of these polyphenols on mitochondrial biogenesis and fatty acid oxidation were analysed. Myotubes from healthy donors were cultured for 24 h with either 0.1 μM of RSV or with 10 μM of Q. Glucose metabolism, such as glycogen synthesis, glucose oxidation, and lactate production, were measured with D[U-14C]glucose. β-oxidation using [1–14C]palmitate as well as the expression of key metabolic genes and proteins by Real Time PCR and Western blot were also assessed. Although RSV and Q increased pgc1α expression, they did not significantly change either glucose oxidation or β-oxidation. Q increased AMPK, insulin receptor substrate 1 (IRS-1), and AS160 phosphorylation in basal conditions and glycogen synthase kinase 3 (GSK3β) in insulin-stimulated conditions. RSV tended to increase the phosphorylation rates of AMPK and GSK3β. Both of the polyphenols increased insulin-stimulated glycogen synthesis and reduced lactate production in human myotubes. Thus, physiological doses of RSV or Q may exhibit anti-diabetic actions in human myotubes.


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