Effects of Glucagon

The in vitro effects of glucagon treated to inactivate insulin contamination thus appear to resemble qualitatively those of norepinephrine and epinephrine. 

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Glucagon. Also a peptide hormone, glucagon is produced by a-cells of the islets of Langerhans. The overall effects of glucagon include ... 

Metabolic pathway Target tissue Effect of insulin Effect of glucagon... 

The first phosphatase step is very important FBPase converts fructose,1-6-bisphos-phate into fructose-6-phosphate under allosteric control of several factors but during fasting, glucagon-induced regulation is crucial. One effect of glucagon stimulation of liver cells is to reduce the concentration of fructose-2,6-bisphosphate, an isomer that activates PFK-1 and is itself synthesized by PFK-2 when fructose-6-phosphate concentration rises... 

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.

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.

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 ...

Although many cells in the body express the insulin receptor, its most important targets are skeletal muscle fibres, hepatocytes and adipocytes, where it often antagonizes the effects of glucagon (Table 8.1). The most potent known stimulus of pancreatic insulin release is an increase in blood glucose levels, often occurring after meal times. Insulin orchestrates a suitable metabolic response to the absorption of glucose and other nutrients in a number of ways ... 

The sulfonylureas promote insulin secretion. They block the K+ channels of the pancreatic beta cell membrane causing the beta cell to remain depolarized which promotes insulin secretion. They also antagonize the effects of glucagon and potentiate the action of insulin in target tissues. However, some pancreatic beta cell responsiveness must exist for... 

TABLE 23-4 Effects of Glucagon on Blood Glucose Production and Release of Glucose by the Liver... 

Effects on lipid metabolism Glucagon favors hepatic oxidation of fatty acids and the subsequent formation of ketone bodies fan acetyl CoA. The lipolytic effect of glucagon in adipose tissue is minimal in humans. 

Figure 17-20 The interlocking pathways of glycolysis, gluconeogenesis, and fatty acid oxidation and synthesis with indications of some aspects of control in hepatic tissues. (— ) Reactions of glycolysis, fatty acid degradation, and oxidation by the citric acid cycle. ) Biosynthetic pathways. Some effects of insulin via indirect action on enzymes , 0, or on transcription 0/ 0. Effects of glucagon , .

The same protein kinase that phosphorylates glycogen phosphorylase and glycogen synthase does not phosphorylate the enzymes of pseudocycle II. Rather an enzyme gets phos-phorylated that catalyzes the synthesis of a potent allosteric effector of the two relevant enzymes, phosphofructokinase and fructose bisphosphate phosphatase. In the liver the un-phosphorylated form this enzyme synthesizes fructose-2,6-bisphosphate. Phosphorylation converts it into a degradative enzyme for the same compound. Fructose-2,6-bisphosphate is an activator of phosphofructokinase and an inhibitor of fructose bisphosphate phosphatase. As a result the net effect of glucagon on pseudocycle II is to stimulate fructose bisphosphate phosphatase while inhibiting phosphofructokinase (see table 12.2 and fig. 12.30). 

Glucagon is considered to be the hormonal antagonist of insulin.29,35 The primary effect of glucagon is to increase blood glucose to maintain normal blood glucose levels and to prevent hypoglycemia.35,93 Glucagon pro-... 

Glucagon has a number of effects on various aspects of hepatocyte metabolism. Many of these are covered in other parts of this treatise. The focus of our present attention is the identity of the intracellular messengers which mediate the effects of glucagon. In considering this question, it is first necessary to recognize that different mechanisms operate when cells are exposed to low or high concentrations of glucagon. 

Fig. 2. Effects of glucagon (10-10, 5 x 10 10 and 10-9 M) on cAMP levels, cAMP-dependent protein kinase activity ratio and phosphorylase a activity in isolated rat hepatocytes. Reproduced from Ref. 58 by permission of the author and publisher.

Early studies of the stimulatory effects of glucagon on hepatic gluconeogenesis using different gluconeogenic substrates and measuring the changes in the concentrations of intermediary metabolites identified the substrate cycles between pyruvate and P-enolpyruvate and between fructose-1,6-P2 and fructose-6-P as major sites of... 

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