Glucagon in liver

Figure 23.3 Actions of glucagon in liver that lead to a rise in blood... 

NB Production ofF 2,6-bisP is stimulated by insulin in liver, and by high fructose 6-phosphate concentrations in skeletal muscle. F 2,6-bisP is depleted by glucagon in liver, and by low fructose 6-phosphate concentrations in skeletal muscle. 

Primary signals Insulin turns off. Glucagon turns on. Acetyl-CoA turns on. Phosphorylation turns on in liver. 

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 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. 

Effect of insulin and glucagon on the synthesis of key enzymes of glycolysis in liver. 

The Coris found that the interconversion of phosphor-ylases a and b is catalyzed by another enzyme, and subsequent work by Earl Sutherland showed that this process is under hormonal control. In muscle, conversion of phosphorylase b to a is stimulated by epinephrine in liver, it is stimulated by both epinephrine and the pancreatic hormone glucagon. The structural basis for the difference between the two forms of phosphorylase remained unknown until the late 1950s, when Edwin Krebs and Edmund Fischer showed that phosphorylase a has a phosphate on serine 14. This phosphate is absent in the b form of the enzyme. Krebs and Fischer also showed that the kinase that catalyzes the addition of the phosphate is itself regulated by a phosphorylation catalyzed by another enzyme, the cAMP-dependent protein kinase ... 

Fructose-2,6-bisphosphate is a potent activator of the liver phosphofructokinase (PFK-1) and a potent inhibitor of liver fructose-1,6-bisphosphate phosphatase (FBPase-1). Fructose-2,6-bisphosphate is the product of a second phosphofructokinase (PFK-2) and is hydrolyzed to fructose-6-phosphate by FBPase-2. The activities of PKF-2 and FBPase-2 reside on a single, bifunctional protein in liver. The bifunctional protein is under glucagon control imposed via cAMP. 

Insulin is an endogenous hormone produced by fi-cells of islets of Langerhans of the pancreas, which consist of two chains of amino acids. It is required to be administered by a parenteral routes as it is destroyed when given orally. Insulin is used for the control of IDDM and in the emergency management of diabetic ketoacidosis.30 Insulin promotes the intracellular uptake of potassium and is used in hyperkalemia. Baker et al.31 have used insulin and glucagon in the treatment of liver disorders. Recent evidence indicates that the effects of insulin with glucose and potassium in ischemic heart disease have proved beneficial.32 It also is used in acute myocardial infarction.32... 

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