Insulin activity

Figure 21-6. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation.The enzyme is inactivated by phosphorylation by AMP-activated protein kinase (AMPK), which in turn is phosphorylated and activated by AMP-activated protein kinase kinase (AMPKK). Glucagon (and epinephrine), after increasing cAMP, activate this latter enzyme via cAMP-dependent protein kinase. The kinase kinase enzyme is also believed to be activated by acyl-CoA. Insulin activates acetyl-CoA carboxylase, probably through an "activator" protein and an insulin-stimulated protein kinase.

Lipogenesis is regulated at the acetyl-CoA carboxylase step by allosteric modifiers, phosphorylation/de-phosphorylation, and induction and repression of enzyme synthesis. Citrate activates the enzyme, and long-chain acyl-CoA inhibits its activity. Insulin activates acetyl-CoA carboxylase whereas glucagon and epinephrine have opposite actions. 

The diabetic rats were treated with 18 IU of bovine insulin imbibed into polyacid resins b.i.d. orally using 1 cc syringes and gavage tubes. After 14 days of treatment the rats were sacrificed about 1.5 hours after the last dose. Blood samples were taken and assayed for immunoactive insulin activity (Amersham-Searie RIA kit) and serum glucose levels (glucose oxidase colorimetric assay, Sigma 510 Glucose Kit). 

When diabetic rabbits (24) were treated with 50 IU of bovine insulin imbibed at 50 mg/g poly (acrylic acid) (Figure 14) no reduction in serum glucose over that achieved by the dry blend control could be detected. Pretreatment of the animals with oral doses of either a penetration enhancer, sodium taurocholate, or a protease inhibitor, aproteinin, failed to improve the insulin activity. One possible explanation for this unexpected lack of activity might be that the diseased animals exhibit impaired ileal absorption of fluids (25). 

Insulin Active tris-Phosphorylated Release of activation loop by p l yr1162... 

Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW and Shulman GI. 2002. Mechanism by which fatty acids inhibit insulin activation ofinsuhn receptor substrate-1 (IRS-l)-associatedphosphatidylinositol 3-kinase activity in muscle. J Biol Chem 27 277(52) 50230-50236. 

The starting material loaded onto the column is fairly pure (—92 per cent), and this step yields a final product of approximately 99 per cent purity. Over 95 per cent of the insulin activity loaded onto the column can be recovered. A single column run takes in the order of 1 h. 

Protein kinase A also phosphorylates PDE2, PDE3 and PDE4, although the function of these enzymes is thereby influenced in different ways. Only the particulate form of PDE2 is phosphorylated by the protein kinase, but this is not known to influence enzyme activity. Phosphorylation of PDE3 by protein kinase A in rat adipocytes stimulates the catalytic activity of the enzyme. PDE3 in these cells is also phosphorylated and activated by an insulin-activated kinase, which has not yet been identified with certainty. 

It was reported in 1980 that vanadate showed insulin activity (415) at about the same time it was demonstrated that vanadate is reduced to vanadium(IV) in vivo (416,417). Subsequently it was found that orally administered vanadate restored blood glucose levels and cardiac function to normal in rats (418). Vanadyl sulfate, less toxic than vanadate, also lowers blood sugar levels and ameliorates cardiac... 

Insulin activates PFK-2 (via the tyrosine kinase receptor and activation of protein phosphatases), which converts a tiny amovmt of fructose 6-phosphate to fructose 2,6-bisphosphate (F2,6-BP). F2,6-BP activates PFK-1. Glucagon inhibits PFK-2 (via cAMP-dependent protein kinase A), lowering F2,6 BP and thereby inhibiting PPK-1. 

Answer C. Only PFK-2 will be insulin-activated In the postprandial period. 

Rate-limiting Citrate activates, insulin activates Fatty acid synthase (requires NADPH)... 

Figure 6.34 Effects of glucagon and insulin on the cyclic AMP level. Glucagon increases the activity of adenylate cyclase, which increases the concentration of cyclic AMP whereas insulin activates the phosphodiesterase which hydrolyses cyclic AMP to form AMP. Cyclic AMP activates protein kinase A.

Metabolism. The nucleotide cAMP (adenosine 3, 5 -cyclic monophosphate) is synthesized by membrane-bound adenylate cyclases [1] on the inside of the plasma membrane. The adenylate cyclases are a family of enzymes that cyclize ATP to cAMP by cleaving diphosphate (PPi). The degradation of cAMP to AMP is catalyzed by phosphodiesterases [2], which are inhibited by methylxanthines such as caffeine, for example. By contrast, insulin activates the esterase and thereby reduces the cAMP level (see p. 388). 

Combination of the A and B chains 8,11 involved deprotection of Cys(Bzl), Lys(Tos), and Arg(Tos) or Arg(N02) by sodium in liquid ammonia and slow air oxidation to form the intrachain A6-An disulfide and the two interchain A7-B7 and A20-B19 disulfides. In some experiments, the 5-sulfonates were utilized for combination of the chains. All three syntheses produced material with insulin activity in the mouse convulsion assay or the glucose oxidation assay. 

Khan, F.A. Goforth, P.B. Zhang, M. Satin, L.S. Insulin activates ATP-sen-sitive K channels in pancreatic b-cells through a phosphatidylinositol 3-kinase-dependent pathway. Diabetes, 50, 2192-2198 (2001)... 

Insulin also stimulates the storage of excess fuel as fat (Fig. 23-26). In the liver, insulin activates both the oxidation of glucose 6-phosphate to pyruvate via glycolysis and the oxidation of pyruvate to acetyl-CoA. If not oxidized further for energy production, this acetyl-CoA is used for fatty acid synthesis in the liver, and the fatty acids are exported as the TAGs of plasma lipoproteins (VLDLs) to the adipose tissue. Insulin stimulates TAG synthesis in adipocytes, from fatty acids released... 

AMP is related to certain mental diseases and may be involved in the action of tranquilizers and antidepressant drugs (60). Whether the ability of diuretic agents such as ethacrynic acid and chlorthalidone to inhibit the enzyme in kidney (68) is related to their diuretic action is also not known. It has been suggested that inhibition of diesterase by diazoxide (59) may explain the hyperglycemic activity of this agent. Several materials are known to activate the enzyme. Imidazole produces strong activation of the enzyme from mammalian tissues (36, 38, 42) but not from E. coli (41). It has been reported (61) that insulin activates the beef heart enzyme in vitro, but it is not known if this has relevance... 

This study has revealed that 2-azetidinones are effective as antihyperglycemic agents and might act either through increased utilization of glucose or through increased insulin activity or induction of glycogen synthetase enzyme. 

Insulin activity is increased by anabolic/androgenic steroids. This means dosages were often reported as lower (less exogenous insulin) when stacking with AAS and other anabolic substances. 

Vanadium compounds interact with insulin-activated signal transduction pathways by inhibiting protein phosphatases, as shown in Figure 11.1 for the insulin... 

Another AT2 pathway linked to apoptosis leads to a stimulation of a soluble protein tyrosine phosphatase, SHP-1, an enzyme that associates with insulin receptor substrate (IRS)-2 (Cui et al. 2002). Overexpression of a dominant negative form of SHP-1 in PC12W cells has been found to attenuate AT2 receptor-mediated inhibition of insulin signaling. Since insulin activates Akt, it is interesting that the mechanism of apoptosis in the angiotensin II-treated PC12W cell involves the dephosphorylation and inactivation of Akt. In NIE-115 neuroblastoma cells,... 

Nakai, N., Y. Sato, Y. Oshida, N. Fujitsuka, A. Yoshimura, and Y. Shimomura (1999). Insulin activation of pyruvate dehydrogenase complex is enhanced by exercise training. Metabolism Clin. Exper. 48 865-869. 

Answer The amplification results from catalysts activating catalysts—including protein kinases that act in enzyme cascades. Two molecules of insulin activate an insulin receptor dimer for a finite period, during which the receptor phosphorylates many molecules of IRS-1. Through a series of interactions with other proteins (including Grb2, Sos, Ras), IRS-1 activates Raf, which phosphorylates and activates many molecules of MEK, each of which phosphorylates and activates many molecules of ERK. Each activated ERK phosphorylates and activates several molecules of a transcription factor, and each of these stimulates the transcription of multiple copies of mRNA for specific genes. Each mRNA can direct the synthesis of many copies of the protein it encodes. (See Fig. 12-15.)... 

Brownsey, R.W., Denton, R.M. 1982. Evidence that insulin activates fat-cell acetyl-CoA carboxylase by increased phosphorylation at a specific site. Biochem. J. 202, 77-86. 

Gins may. also contribute to the mechanism whereby insulin activates glucose transport in adipocytes and heart. This has been suggested to be a two-step process where the first step involves the recruitment of inactive glucose carriers from an internal vesicle pool to the plasma membrane and the second step involves the activation of the newly inserted carriers in the plasma membrane (vide supra). It is possible that this second step may be controlled by Gins. The reasons for thinking that this may be so are related to observations that, under certain conditions, glucagon... 

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