Glucagon degradation

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. 

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. 

Primary signals Insulin turns synthesis on, degradation off. Glucagon turns synthesis off, degradation on. Epinephrine turns synthesis off, degradation on. Phosphorylation turns synthesis off, degradation on. 

Starvation ( ] glucagon i insulin) Glycogen exhaustion Diabetes ( f glucagon [ insulin) Glycogen degradation Excitement ( ] epinephrine). Glycogen degradation... 

Starvation (f glucagon j insulin) Extensive protein degradation Diabetes ( glucagon insulin) Protein degradation Excitement ( epinephrine)-. Protein degradation... 

R. P. Pauly, F. Rosche, M. Wermann, C. H. McIntosh, R. A. Pederson, and H. U. Demuth. Investigation of Glucose-Dependent Insulinotropic Polypeptide-(l-42) and Glucagon-like Peptide-1-(7-36) Degradation In Vitro by Dipeptidyl Peptidase IV Using Matrix-Assisted... 

Biosynthesis and degradation of glycosaminoglycans biosynthesis of collagen, mineralization and demineralization of bone. Fatty acid synthesis and triglyceride storage in adipocytes promoted by insulin and triglyceride hydrolysis and fatty acid release stimulated by glucagon and adrenaline (epinephrine). 

Improved stability with simultaneous preservation of activity has been demonstrated with analogues of glucagon-like peptide-1 and gastric inhibitory polypeptide, two hormones that stimulate the release of insulin. Glucagon-like peptide-1 (GLP-1) is a 30-residue gastrointestinal hormone, ami-dated at the C-terminus that has potential as a treatment for type-2 diabetes. However, GLP-1 is rapidly degraded by dipeptidyl-peptidase IV (EC... 

Hydroxy-3-methylglutaryl (HMG)-CoA reductase on the smooth endoplasmic reticulum (SER) is the rate-limiting enzyme. Insulin acth"ates the enzyme (dephosphorylation), and glucagon inhibits it. Mevalonate is the product, and the statin drugs competitively inhibit the enzyme. Cholesterol represses the expression o the HMG-CoA reductase gene and also increases degradation of the enzyme. 

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). 

This zinc-dependent enzyme [EC 3.4.24.56], a member of the peptidase family M16, catalyzes the degradation of insulin, glucagon, and other polypeptides. 

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