Glucose in skeletal muscle

The term ketone bodies refers primarily to two compounds acetoacetate and P-hydroxy-butyrate, which are formed from acetyl-CoA when the supply of TCA-cycle intermediates is low, such as in periods of prolonged fasting. They can substitute for glucose in skeletal muscle, and, to some extent, in the brain. The first step in ketone body formation is the condensation of two molecules of acetyl-CoA in a reverse of the thiolase reaction. 

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. 

Lactate produced by anaerobic metabolism in skeletal muscle passes to liver, which uses it to synthesize glucose, which can then return to muscle (the Cori cycle). 

To gain further insight into the mechanisms involved in defective insulin-stimulated glucose uptake in skeletal muscle of insulin-resistant subjects, the possible role of IMCL in the pathogenesis of skeletal muscle insulin resistance and type 2 diabetes mellitus was explored by comparing insulin sensitivity (GIR) and IMCL content of insulin-resistant and insulin-sensitive offsprings of patients with type 2 diabetes. Twenty-six healthy subjects were included in the first study, 13 of them classified as insulin-sensitive and further 13 as insulin-resistant. Metabolic and anthropometric data are given in Table 4. 

In skeletal muscle, glucose transport is non-equilibrium, so that an increase in activity of the transporter increases glucose utilisation. Factors that increase the activity of the transporter (e.g. the number of transporter molecules) in the membrane are insulin and sustained physical activity. In contrast, the hormone cortisol decreases the number of transporters in the membrane. This decreases glucose uptake and is one of the effects of cortisol that helps to maintain the normal blood glucose level (Chapter 12). 

Figure 6.14 An increase in the rate of glucose transport, in response to insulin, which increases the rate of glycolysis. This is achieved by increasing the concentrations of all the intermediates in the pathway, indicated by the arrows adjacent to the intermediates. Insulin, physical activity or a decrease in the ATP/ADP concentration ratio all result in increased rates of glucose transport in skeletal muscle. Insulin increases the rate about fivefold, physical activity about 50-fold.

Mechanism of Action An antidiabetic that improves target-cell response to insulin without increasing pancreatic insulin secretion. Decreases hepatic glucose output and increases insulin-dependent glucose utilization in skeletal muscle. Therapeutic Effect Lowers blood glucose concentration. 

The glucose 6-phosphate formed from glycogen in skeletal muscle can enter glycolysis and serve as an energy source to support muscle contraction. In liver,... 

The main stores of glycogen in the body are found in skeletal muscle, where they serve as a fuel reserve for the synthesis of ATP during muscle contraction, and in the liver, where glycogen is used to maintain the blood glucose concentration, particularly during the early stages of a fast. 

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