Principles of Biochemistry Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Hormones
Glucagon is a hyperglycemic hormone of the pancreas

Glucagon, also a polypeptide hormone, is secreted by the A Cells of the pancreatic islets and functionally related cells in the gastrointestinal tract. It is a single-chain polypeptide consisting of 29 amino acid residues with a Molecular Weight of 3,500 (Fig. 25-19). Recent studies have shown that glucagon, much like Insulin, has two inactive precursors: proglucagon and preproglucagon. The latter contains an N-terminal signal polypeptide sequence that is cleaved in two stages, ultimately yielding proglucagon.

Glucagon raises Blood glucose concentration, meaning its physiological action is antagonistic to that of insulin (Table 25-6). This hyperglycemic effect is achieved through two distinct mechanisms. First, glucagon stimulates hepatic Glycogenolysis, releasing glucose into the bloodstream via a mechanism analogous to that of epinephrine. Specific glucagon receptors are located on the outer surface of Cell/30.html">The Plasma Membrane of Liver cells. Upon binding to these receptors, glucagon triggers an Amplification cascade in the plasma membrane, similar to the action of epinephrine (Fig. 25-11). Second, unlike epinephrine, glucagon inhibits the glycolytic breakdown of glucose to lactate. This effect results from the indirect inhibition of the hepatic (L-type) isozyme of Pyruvate kinase (Section 15.13), which is involved in Glycolysis. Glucagon also differs from epinephrine in that it has a significantly more prolonged duration of action and does not increase Heart rate or blood pressure.

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Fig. 25-19. Structures of bovine proglucagon and glucagon. Glucagon consists of 29 amino acid residues and has a molecular weight of 3,500. It is generated through the Enzymatic Cleavage of eight amino acid residues (shown in red) from the C-terminus of proglucagon.