Glucagon action

Stimulation of glycogen breakdown involves consumption of molecules of ATP at three different steps in the hormone-sensitive adenylyl cyclase cascade (Figure 15.19). Note that the cascade mechanism is a means of chemical amplification, because the binding of just a few molecules of epinephrine or glucagon results in the synthesis of many molecules of cyclic / MP, which, through the action of c/ MP-dependent protein kinase, can activate many more molecules of phosphorylase kinase and even more molecules of phosphorylase. For example, an extracellular level of 10 to 10 M epinephrine prompts the for-... 

Antidiabetic Drugs other than Insulin. Table 3 Actions of the incretin hormones GIP (glucose-dependent insulinotropic polypeptide, gastric inhibitory peptide) and GLP-1 (glucagon-like peptide-1)... 

Cyclic AMP (cAMP) (Figure 18-5) is formed from ATP by adenylyl cyclase at the inner surface of cell membranes and acts as an intracellular second messenger in response to hormones such as epinephrine, norepinephrine, and glucagon. cAMP is hydrolyzed by phosphodiesterase, so terminating hormone action. In hver, insulin increases the activity of phosphodiesterase. 

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. 

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.

When the actions of one hormone oppose the effects of another, the result is antagonism. For example, insulin decreases blood glucose and promotes the formation of fat. Glucagon, on the other hand, increases blood glucose and promotes the degradation of fat. Therefore, the effects of insulin and glucagon are antagonistic. 

Gutniak, M.K., Svartberg, J., Hellstrom, P.M. et al. (2001) Antidiabetogenic action of glucagon-like peptide-1 related to administration relative to meal intake in subjects with type 2 diabetes. Journal of Internal Medicine, 250, 81-87. 

The answer is a. (Hardman, p 1510.) Although the mechanism of action of metformin and other biguanicies is unclear, biguanides virtually never cause hypoglycemia They operate independently of pancreatic p cells but are not useful in insulin-dependent diabetes mellitus (IDDM). Some possible mechanisms of action are direct stimulation of glycolysis in peripheral tissues, increased sensitivity to insulin, and reduction of glucagon levels. 

The answer is b. (Hardman, p 1507. Katzung, pp 723-724J Three proposed mechanisms for sulfonylurea action are (1) the release of insulin from pancreatic cells, (2) reduction of serum glucagon levels, and (.3) increased binding of insulin to tissue receptors. On binding to a specific receptor that is associated with a K channel in cell membranes, sulfo-nylureas inhibit K efflux, which causes influx of Ca followed by release of preformed insulin. 

Drucker, D. 2002. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 122(2), 531-544. 

Glucagon is a second pancreatic hormone that, like insulin, influences carbohydrate metabolism. However, most of its actions oppose those of insulin. The enkephalins and endorphins are the body s natural painkillers they are thought to be responsible for runner s high. These, among many others, are proteins or are closely related to them. 

Figure 12.13 Action and effects of glucagon. Glucagon binds to its receptor on the plasma membrane of the liver which activates adenyl cyclase. The resultant cyclic AMP activates protein kinase which results in phosphorylation and activation of ...

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