Glucagon mechanism

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-... 

Figure 26-4. Possible mechanisms in the regulation of cholesterol synthesis by HMG-CoA reductase. Insulin has a dominant role compared with glucagon. Asterisk See Figure 18-6.

Joshi AB, Sawai M, Kearney WR, et al. Studies on the mechanism of aspartic acid cleavage and glutamine deamidation in the acidic degradation of glucagon. /. Pharm. Sci. 2005 94 1912-1927. 

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. 

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. 

Figure F -6. Cortisol and Glucagon Stimulate Gluconeogenesis Through Enhancer Mechanisms...

Insulin stimulates and glucagon inhibits PFK-1 in hepatocytes by an indirect mechanism involving PFK-2 and fructose 2,6-bisphosphate (Figure 1-12-3). 

Insulin, which is formed in the B cells of the pancreas, has both endocrine and paracrine effects. As a hormone with endocrine effects, it regulates glucose and fat metabolism. Via a paracrine mechanism, it inhibits the synthesis and release of glucagon from the neighboring A cells. 

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