Skeletal muscle glycogenolysis

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

These cascades of reactions need time in the range of seconds synaptic transmission through GPCRs is slow. All further postsynaptic changes depend on the type of postsynaptic cell. For example activation of 32-adrenoceptors causes in the heart an increase of the rate and force of contraction in skeletal muscle glycogenolysis and tremor in smooth muscle relaxation in bronchial glands secretion and in sympathetic nerve terminals an increase in transmitter release. 

Spriet, L.L., Soderlund, K., Bergstrom, M., Hultman, E. (1987b). Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men. J. Appl. Physiol. 62, 616-621. 

Isoproterenol is the most potent stimulant of skeletal muscle glycogenolysis, followed by epinephrine and norepinephrine. (3z-Adrenoceptors mediate muscle glycogenolysis. Stimulation of skeletal muscle glycogenolysis will raise blood lactic acid levels rather than blood glucose levels because skeletal muscle lacks the enzyme glucose-6-phosphatase, which catalyzes the conversion of glucose-6-phosphate to glucose. 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Epinephrine stimulates glycogenolysis in skeletal muscle, whereas glucagon does not because of absence of its receptors. 

Glycogen phosphorylase isoenzymes have been isolated from liver, brain and skeletal muscle. All forms are subject to covalent control with conversion of the inactive forms (GP-b) to the active forms (GP-a) by phosphorylation on specific serine residues. This phosphorylation step, mediated by the enzyme phosphorylase kinase, is initiated by glucagon stimulation of the hepatocyte. Indeed, the same cAMP cascade which inhibits glycogen synthesis simultaneously stimulates glycogenolysis, giving us an excellent example of reciprocal control. 

Metabolic effects. P-Receptors mediate increased conversion of glycogen to glucose (glycogenolysis) in both liver and skeletal muscle. From the liver, glucose is released into the blood. In adipose tissue, triglycerides are hydrolyzed to fatty acids lipolysis, mediated by P3-receptors), which then enter the blood (C). The metabolic effects of catecholamines are not amenable to therapeutic use. 

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

Four different phosphatases in skeletal muscle catalyze the dephosphorylation of the various enzymes involved in glycogenolysis. Their activities are controlled by various inhibitors. 

Serebrennikova, T.P., Silkina, E.N., Shmelev, V.K., Morozova, A.L. and Nesterov, V.P. (1991). The regulation of glycogenolysis in skeletal muscle of annular bream during intensive performance as dependent on temperature (In Russian). Zhumal Evolutsionnoy Biokhimii i Physiologii 27,427-431. 

The major substrate of phosphorylase b kinase is phosphorylase b which is phos-phorylated on a single serine residue at position 14, resulting in conversion to the more catalytically active form phosphorylase a [70], Phosphorylation of skeletal muscle phosphorylase also results in conversion of the Mr 200000 dimeric b form to the Mr 400000 tetrameric a form, whereas phosphorylation of the liver enzyme does not alter its dimeric structure [82]. Phosphorylase a is much less dependent than phosphorylase b upon the allosteric activator AMP [82], Since the activity of phosphorylase is rate-limiting for glycogen breakdown, its activation by phosphorylase b kinase results in enhanced glycogenolysis and glucose release from the liver. 

Contract sphincters of GI tract. Increases lipolysis in adipose tissue, increases anabolism in skeletal muscle, increase glycogenolysis and gluconeogenesis. 

Rennie, M.J. Hoiloszy, J.O. ( 1977) Inuibition of glucose uptake and glycogenolysis by availability of oleate in well-oxygenated perfused skeletal muscle. Biochem. J. 168 ... 

The primary mechanism of terbutaline is the stimulation of adenylcyclase, which catalyzes cyclic adenosine monophosphate (AMP) from adenosine triphosphate (ATP). In the liver, buildup of cyclic AMP stimulates glycogenolysis and an increase in serum glucose. In skeletal muscle, this process results in increased lactate production. Direct stimulus of sodium/potassium AT-Pase in skeletal muscle produces a shift of potassium from the extracellular space to the intracellular space. Relaxation of smooth muscle produces a dilation of the vasculamre supplying skeletal muscle, which results in a drop in diastolic and mean arterial pressure (MAP). Tachycardia occurs as a reflex to the drop in MAP or as a result of Pi stimulus. )Si-Adrenergic receptors in the locus ceruleus also regulate norepinephrine-induced inhibitory effects, resulting in agitation, restlessness, and tremor. 

Glycogenolysis and a negative nitrogen balance occur with the onset of fever. These are prompted by the typically decreased food intake and wasting of skeletal muscle that accompany fever. Although there is usually an increase in the blood volume with fever, the serum concentrations of creatinine and urate are usually increased. Aldosterone secretion is increased with retention of sodium and chloride. Secretion of antidiuretic hormone also contributes to the retention of water by the kidneys. Increased synthesis of protein... 

F-2,6-BE Thus, F-2,6-BP levels are decreased and phosphofructokinase activity is decreased. In liver and muscle, F-2,6-BP is the major allosteric activator of phosphofructokinase. In skeletal muscle, however, the kinase responsible for the synthesis of F-2,6-BP is activated, not inhibited, by cyclic AME Thus, muscle sees an increase in glycolysis following epinephrine stimulation, while the liver experiences a decrease in glycolytic activity. In both tissues, glycogen phosphorylase is activated and glycogenolysis occurs. Under these conditions, glucose is utilized in muscle for ATP production relative to contractile activity, while the liver produces glucose for export to the blood. 

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