Adipose glucagon

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Otfier fiormones accelerate tfie release of free fatty acids from adipose tissue and raise tfie plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25—8). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive hpase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. 

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.

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

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. 

Answer C. Severe hypoglycemia lowers the insulin level and increases glucagon. This would favor fatty acid release from the adipose and ketogenesis in the liver. 

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

Figure 7.14 Regulation of rate of fatty acid oxidation in tissues. Arrows indicate direction of change (i) Changes in the concentrations of various hormones control the activity of hormone-sensitive lipase in adipose tissue (see Figure 7.10). (ii) Changes in the blood level of fatty acid govern the uptake and oxidation of fatty acid, (iii) The activity of the enzyme CPT-I is controlled by changes in the intracellular level of malonyl-CoA, the formation of which is controlled by the hormones insulin and glucagon. Insulin increases malonyl-CoA concentration, glucagon decrease it. Three factors are important TAG-lipase, plasma fatty acid concentration and the intracellular malonyl-CoA concentration.

Glucagon is secreted by the a-cells in the Islets of Langerhans in response to a decrease in the concentration of blood glucose. It binds to a receptor in liver and adipose tissue which activates adenyl cyclase and raises the innacel-lular level of cAMP, which activates protein kinase A (Figure 12.13). 

The function of glucagon is to respond rapidly to an acute fall in the blood glucose level by stimulating glucose release by the liver and fatty acid release by adipose tissue. 

Figure 16.4 Effect of several hormones on the glucose/fatty acid cycle. Catecholamines, glucagon and growth hormone stimulate lipolysis in adipose tissue and hence antagonise the effects of insulin.

The endocrine pancreas responds to this by altering its hormone release—there is an increase in insulin secretion and a reduction in glucagon secretion. The increase in the insu-lin/glucagon quotient and the availability of substrates trigger an anabolic phase in the tissues—particularly liver, muscle, and adipose tissues. 

In adipose tissue, glucagon triggers lipoly-sis, releasing fatty acids and glycerol. The fatty acids are used as energy suppliers by many types of tissue (with the exception of brain and erythrocytes). An important recipient of the fatty acids is the liver, which uses them for ketogenesis. 

The metabolic disruption In type 1 diabetes is due to both the absence of insulin action and unopposed glucagon action In liver, muscle, and adipose tissues. 

In the absence of insulin and in response to glucagon stimulation, triacylglycerol degradation in adipose tissue runs unabated and the flood of fatty acids reaching the liver leads to ketone body synthesis and packaging of some triacylglycerols into VLDLs. 

Dysfunction of fat metabolism is caused by the low insulin/glucagon ratio, which stimulates fat mobilization by adipose tissue, flooding the liver with fatty acids and raising intracellular acetyl CoA levels. 

When blood glucose levels drop between meals, glucagon release activatescAMP-dependent protein kinase (FKA), which phoe phorylates and inactivates ACC. The concentration of malonyl-CoA falls, the inhibition of fatty acid entry into mitochondria is relieved, and fatty acids enter the mitochondrial matrix and become the major fuel. Because glucagon also triggers the mobilization of fatty acids in adipose tissue, a supply of fatty acids begins arriving in the blood. 

T Fatty acid mobilization (adipose tissue) T Glucagon secretion i Insulin secretion... 

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