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Activity Of Which Of The Following Pathways Is Increased As A Result Of Increased Insulin?

Metabolic Pathways

Metabolic Pathways

There are three groups of molecules that form the core building blocks and fuel substrates in the body: carbohydrates (glucose and other sugars); proteins and their constituent amino acids; and lipids and their constituent fatty acids. The biochemical processes that allow these molecules to be synthesized and stored (anabolism) or broken down to generate energy (catabolism) are referred to as metabolic pathways. Glucose metabolism involves the anabolic pathways of gluconeogenesis and glycogenesis, and the catabolic pathways of glycogenolysis and glycolysis. Lipid metabolism involves the anabolic pathways of fatty acid synthesis and lipogenesis and the catabolic pathways of lipolysis and fatty acid oxidation. Protein metabolism involves the anabolic pathways of amino acid synthesis and protein synthesis and the catabolic pathways of proteolysis and amino acid oxidation. Under conditions when glucose levels inside the cell are low (such as fasting, sustained exercise, starvation or diabetes), lipid and protein catabolism includes the synthesis (ketogenesis) and utilization (ketolysis) of ketone bodies. The end products of glycolysis, fatty acid oxidation, amino acid oxidation and ketone body degradation can be oxidised to carbon dioxide and water via the sequential actions of the tricarboxylic acid cycle and oxidative phosphorylation, generating many molecules of the high energy substrate adenosine triphosphate (ATP). Interplay between metabolic pathways The interplay between glucose metabolism, lipid metabolism, ketone body metabolism and protein and amino acid metabolism is summarized in Figure 1. Amino acids can be a source of glucose synthesis as well as energy production and excess glucose that is not required for energy production can be stored as glycogen or metabo Continue reading >>

Insulin Signal Transduction Pathway

Insulin Signal Transduction Pathway

The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones. When carbohydrates are consumed, digested, and absorbed the pancreas senses the subsequent rise in blood glucose concentration and releases insulin to promote an uptake of glucose from the blood stream. When insulin binds to the insulin receptor, it leads to a cascade of cellular processes that promote the usage or, in some cases, the storage of glucose in the cell. The effects of insulin vary depending on the tissue involved, e.g., insulin is most important in the uptake of glucose by muscle and adipose tissue. This insulin signal transduction pathway is composed of trigger mechanisms (e.g., autophosphorylation mechanisms) that serve as signals throughout the cell. There is also a counter mechanism in the body to stop the secretion of insulin beyond a certain limit. Namely, those counter-regulatory mechanisms are glucagon and epinephrine. The process of the regulation of blood glucose (also known as glucose homeostasis) also exhibits oscillatory behavior. On a pathological basis, this topic is crucial to understanding certain disorders in the body such as diabetes, hyperglycemia and hypoglycemia. Transduction pathway[edit] The functioning of a signal transduction pathway is based on extra-cellular signaling that in turn creates a response which causes other subsequent responses, hence creating a chain reaction, or cascade. During the course of signaling, the cell uses each response for accomplishing some kind of a purpose al Continue reading >>

Physiologic Effects Of Insulin

Physiologic Effects Of Insulin

Stand on a streetcorner and ask people if they know what insulin is, and many will reply, "Doesn't it have something to do with blood sugar?" Indeed, that is correct, but such a response is a bit like saying "Mozart? Wasn't he some kind of a musician?" Insulin is a key player in the control of intermediary metabolism, and the big picture is that it organizes the use of fuels for either storage or oxidation. Through these activities, insulin has profound effects on both carbohydrate and lipid metabolism, and significant influences on protein and mineral metabolism. Consequently, derangements in insulin signalling have widespread and devastating effects on many organs and tissues. The Insulin Receptor and Mechanism of Action Like the receptors for other protein hormones, the receptor for insulin is embedded in the plasma membrane. The insulin receptor is composed of two alpha subunits and two beta subunits linked by disulfide bonds. The alpha chains are entirely extracellular and house insulin binding domains, while the linked beta chains penetrate through the plasma membrane. The insulin receptor is a tyrosine kinase. In other words, it functions as an enzyme that transfers phosphate groups from ATP to tyrosine residues on intracellular target proteins. Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor. The activated receptor then phosphorylates a number of intracellular proteins, which in turn alters their activity, thereby generating a biological response. Several intracellular proteins have been identified as phosphorylation substrates for the insulin receptor, the best-studied of which is insulin receptor substrate 1 or IRS-1. When IRS-1 is activa Continue reading >>

Signaling Pathways In Insulin Action: Molecular Targets Of Insulin Resistance

Signaling Pathways In Insulin Action: Molecular Targets Of Insulin Resistance

Go to: The insulin receptor Insulin action is initiated through the binding to and activation of its cell-surface receptor, which consists of two α subunits and two β subunits that are disulfide linked into an α2β2 heterotetrameric complex. Insulin binds to the extracellular α subunits, transmitting a signal across the plasma membrane that activates the intracellular tyrosine kinase domain of the β subunit. The receptor then undergoes a series of intramolecular transphosphorylation reactions in which one β subunit phosphorylates its adjacent partner on specific tyrosine residues. Some evidence suggests that different tyrosine residues account for distinct functions. For example, phosphorylation of COOH-terminal tyrosines mediates the mitogenic actions of insulin. The phosphorylated tyrosines in the juxtamembrane domain may participate in substrate binding, whereas those found within the kinase domain regulate the catalytic activity of the insulin receptor β subunit. Some forms of insulin resistance may involve the receptor itself. Alterations in insulin receptor expression, binding, phosphorylation state, and/or kinase activity could account for many insulin- resistance phenotypes. In addition, it is possible that the selected blockade of distinct phosphorylation sites selectively inhibits certain actions of insulin. In this regard, individuals have been identified with rare genetic defects in the insulin receptor that influence expression, ligand binding, and tyrosine kinase activity. These patients demonstrate severe insulin resistance, manifest as clinically diverse syndromes including the type A syndrome, leprechaunism, Rabson-Mendenhall syndrome, and lipoatropic diabetes (2, 3). The mode of inheritance found in families afflicted with insulin receptor mutat Continue reading >>

Overview Of Insulin Signaling Pathways

Overview Of Insulin Signaling Pathways

​Introduction Insulin is a hormone released by pancreatic beta cells in response to elevated levels of nutrients in the blood. Insulin triggers the uptake of glucose, fatty acids and amino acids into liver, adipose tissue and muscle and promotes the storage of these nutrients in the form of glycogen, lipids and protein respectively. Failure to uptake and store nutrients results in diabetes. Type-1 diabetes is characterized by the inability to synthesize insulin, whereas in type-2 diabetes the body becomes resistant to the effects of insulin, presumably because of defects in the insulin signaling pathway. A. Glucose storage and uptake ​​​The insulin receptor is composed of two extracellular α subunits and two transmembrane β subunits linked together by disulphide bonds (Figure 1). Binding of insulin to the α subunit induces a conformational change resulting in the autophosphorylation of a number of tyrosine residues present in the β subunit (Van Obberghen et al., 2001). These residues are recognized by phosphotyrosine-binding (PTB) domains of adaptor proteins such as members of the insulin receptor substrate family (IRS) (Saltiel and Kahn 2001; Lizcano and Alessi 2002). Receptor activation leads to the phosphorylation of key tyrosine residues on IRS proteins, some of which are recognized by the Src homology 2 (SH2) domain of the p85 regulatory subunit of PI3-kinase (a lipid kinase). The catalytic subunit of PI3-kinase, p110, then phosphorylatesphosphatidylinositol (4,5) bisphosphate [PtdIns(4,5)P2​] leading to the formation of Ptd(3,4,5)P3. A key downstream effector of Ptd(3,4,5)P3 is AKT, which is recruited to the plasma membrane. Activation of AKT also requires the protein kinase 3-phosphoinositide dependent protein kinase-1 (PDK1), which in combination w Continue reading >>

Insulin And Insulin Resistance

Insulin And Insulin Resistance

Go to: Abstract As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the compl Continue reading >>

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