Muscle uptake

Insufficient removal of G6P, leading to a high intracellular free glucose. This blocks the muscle uptake, but as the whole-body uptake continues, at least in healthy people, it requires a yet unknown and precisely timed signal from the muscle to other organs. 

In the patients with ALPE, bone scans showed no muscular uptake of methylene diphosphonate (MDP). However, upper/lower limb muscle uptake of MDP was found in the patients with myoglobinuric acute renal failure (Fig. 75). 

Type 2 DM accounts for as many as 90% of DM cases and is usually characterized by the presence of both insulin resistance and relative insulin deficiency. Insulin resistance is manifested by increased lipolysis and free fatty acid production, increased hepatic glucose production, and decreased skeletal muscle uptake of glucose. )3-Cell dysfunction is progressive and contributes to worsening blood glucose control over time. Type 2 DM occurs when a diabetogenic lifestyle (excessive calories, inadequate exercise, and obesity) is superimposed upon a susceptible genotype. 

A 46-year-old man with hjrpokalemic periodic paralysis and diabetes mellitus had worse muscle weakness after taking acetazolamide, possibly because of reduced muscle uptake of potassium (11). 

Glucose Rednced glycogenolysis and gluconeogenesis and increased glycogen synthesis in liver Increased nptake of glncose and synthesis of glycogen in skeletal muscle Uptake of glucose and synthesis of lipid in fat tissue... 

Obesity, and especially abdominal obesity (section 6.2.3), is strongly associated with insulin resistance and the development of non-insulin-dependent diabetes mellitus (section 10.7). This is largely the result of increased circulating concentrations of non-esterified fatty acids (released from plasma lipoproteins by lipoprotein lipase section 5.5.6.2). Non-esterified fatty acids decrease muscle uptake and utilization of glucose and may also antagonize insulin action. Weight loss results in a considerable improvement in glycaemic control in patients with early non-insulin-dependent diabetes. 

Paton, W. D. M., and Rang, H. P. (1965). The uptake of atropine and related drags by intestinal smooth muscle of the guinea pig in relation to acetylcholine receptors. Proc. R. Soc. Lond. [Biot.] 163 1-44. 

Glucose uptake T AS160 f GLUT4 translocation Muscle... 

Glucose uptake T Myocyte enhancer factor-2 f GLUT4 expression Muscle... 

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... 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

There is weak expression of PPARy in muscle, liver and other tissues, enabling TZDs to support the effects of insulin in these tissues, notably increased glucose uptake in muscle and reduced glucose production in liver. TZDs may also affect nutrient metabolism by skeletal muscle through a direct mitochondrial action that is independent of PPARy. 

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

GLUT4 is a glucose transporter exclusively expressed in tissues with insulin-sensitive glucose uptake (heart, muscle, fat). Under basal conditions, GLUT4 is predominantly located in intracellular vesicles, and is... 

Physiologically muscle-derived NO regulates skeletal muscle contractility and exercise-induced glucose uptake. nNOS is located at the plasma membrane of skeletal muscle and facilitates diffusion of NO to the vasculature to regulate muscle perfusion. 

The exact mechanism by which PPARy ligands affect insulin resistance (improved glucose uptake by peripheral tissues, most notably skeletal muscle) remains unclear. 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

However, repeated excitations do produce a Na and K shift over the muscle membrane, with extrusion of K and uptake of Na. This will change the intracellular ion composition, in spite of the counteracting effect of the Na -K pump. 

Figure 6. Glycogen content in the vastus lateralis muscle as a function of cycling time at 75-80% of maximal oxygen uptake (VO2 max). Data points are mean values from 10 subjects. For each subject, exercise was performed repeatedly in periods of 15 min separated by 15 min rest periods. At the point of exhaustion and muscle fatigue, muscle glycogen stores were depleted. From Bergstrom and Hultman (1967) with permission from the publisher.

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