Insulin fatty acid synthesis increase

Following the administration of insulin to diabetic rats, fatty acid synthesis increases [90,100,102-104] as would be predicted, increases are observed in the citrate cleavage enzyme, fatty acid synthetase, and... 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

Lithium blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin (Kleiner et ah, 1999). This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration. It also inhibits thyrotropin-stimulated adenylate cyclase activity (Kleiner et ah, 1999). Lithium has varying effects on carbohydrate metabolism. Increased and decreased glucose tolerance and decreased sensitivity to insulin have been observed (Van derVelde Gordon, 1969). In animals, lithium decreases hepatic cholesterol and fatty acid synthesis. 

The insulin-induced enhancement of fatty acid synthesis in nonruminant adipose and liver tissues is associated with an increase in the... 

Holland, R., Hardie, D.G. 1985. Both insulin and epidermal growth factor stimulate fatty acid synthesis and increase phosphorylation of acetyl-CoA carboxylase and ATP-citrate lyase in isolated hepatocytes. FEBS Lett. 181, 308-312. 

Carnitine acyltransferase 1 is strongly inhibited by malonyl CoA, andmuscle has both acetyl CoA carboxylase, which forms malonyl CoA, and malonyl CoA decarboxylase, which acts to remove malonyl CoA and relieve the inhibition of carnitine acyl transferase. The two enzymes are regulated in opposite directions in response to insulin, which stimulates fatty acid synthesis and reduces /S-oxidation, and glucagon that reduces fatty acid synthesis and increases p-oxidation (Kerner and Hoppel, 2000 Louet et al., 2001 Eaton, 2002). 

Feeding provokes an increase in the concentration of plasma insulin. This elevation counteracts the effects of glucagon jnenhoned earlier, Insulin also has a variety of effects independent of glucagon action and of cAMP. The most well-known glucagon-independent effect is an increase in glucose transport into muscle for the purpose of glycogen synthesis and into adipose tissue for tire purpose of fatty acid synthesis-... 

D. Decreased insulin levels cause fatty acid synthesis to decrease and glucagon levels to increase. Adipose triacylglycerols are degraded. Fatty acids are converted to ketone bodies in liver a ketoacidosis can occur. There is increased decarboxylation of acetoacetate to form acetone, which causes the odor associated with diabetic ketoacidosis. 

In some tissues, the phosphatase is regulated by hormones. In liver, epinephrine binds to the a-adrenergic receptor to initiate the phosphatidyl inositol pathway (p. 388), causing an increase in Ca" concentration that activates the phosphatase. In tissues capable of fatty acid synthesis, such as the liver and adipose tissue, insulin, the hormone that signifies the fed state, stimulates the phosphatase, increasing the conversion of pyruvate into acetyl Co A. Acetyl CoA is the precursor for fatty acid synthesis (p. 635). In these tissues, the pyruvate dehydrogenase complex is activated to funnel glucose to pyruvate and then to acetyl CoA and ultimately to fatty acids. 

Fig. 9. Reciprocal regulation of fatty acid synthesis and oxidation. Malonyl-CoA, the product of the ACC reaction, inhibits CPT-1, which is localized at the outer mitochondrial membrane and catalyzes the conversion of fatty acyl-CoA to fatty acyl-camitine for mitochondrial fatty acid import and oxidation. At the inner mitochondrial membrane, fatty acyl moieties are converted to CoA thioesters by CPT-II before undergoing -oxidation. ACC is activated by citrate and inhibited by fatty acyl-CoA. AMPK is activated by AMP and the high AMP level reflects the low energy state of the cell. Activation of AMPK in response to increases in AMP involves phosphorylation by an upstream AMPK kinase (AMPKK), the tumor suppressor LKB1, and AMPK is inactivated/dephosphory-lated by protein phosphatase 2A (PP2A), which is first activated by insulin via PI3K/Akt pathway. ACC is dephosphorylated/activated by PP2A and is inactivated upon phosphorylation by AMPK. ACC can also be phos-phorylated/inactivated by PKA. TAG, triacylglycerol FA, fatty acid.

The hver produces ketone bodies by oxidizing free fatty acids to acetyl CoA, which then is converted to acetoacetate and /3-hydroxybutyrate. The initial step in fatty acid oxidation is transport of the fatty acids into the mitochondria. The essential enzyme in this process, acylcarnitine transferase, is inhibited by intramitochondrial malonyl CoA, one of the products of fatty acid synthesis. Normally, insulin inhibits Upolysis, stimulates fatty acid synthesis (thereby increasing the concentration of malonyl CoA), and decreases the hepatic concentration of carnitine these factors aU decrease the production of ketone bodies. Conversely, glucagon stimulates ketone body production by increasing fatty acid oxidation and decreasing concentrations of malonyl CoA. In patients with type 1 DM, insulin deficiency and glucagon in excess provide a hormonal milieu that favors ketogenesis and may lead to ketoacidosis. 

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