Glucagon

The most important peptide produced in the A cells is glucagon. The glucagon gene is composed of six exons and five introns, and the gene is expressed not only in the islet A cells but also in the intestinal L cells and the brain. The glucagon gene codes for a 160-amino acid proglucagon, which is posttranslationally cleaved to several different peptides.50 An important difference exists between the pancreatic A cells and intestinal L cells with regard to cleavage of proglucagon and the final formation of different glucagon-related peptides. Thus, in the pancreatic A cells, three different peptides are formed: glucagon, glicentin-related polypeptide, and a larger peptide, called the major proglucagon fragment, which in its sequence contains the sequence of glucagon-like peptide 1 (GLP-1) and GLP-2. In contrast, in the intestinal L cells, GLP-1 and GLP-2 are formed as separate peptides and, in addition, oxyntomodulin is formed.50

It is known that glucagon gene expression, glucagon synthesis, and glucagon secretion are stimulated by various amino acids (e.g., arginine) and hormones that increase cAMP formation and inhibited by glucose and insulin. Often, the B and A cells are reciprocally regulated, which is illustrated by glucose stimulating the B cells but inhibiting the activity of the A cells. Because insulin and glucagon counteract the effects of each other on glucose metabolism, such a reciprocal regulation is functional. However, some stimuli activate both cell types (e.g., vagal nerve stimulation).51 Such combined activation of both insulin and glucagon cells could be of importance for the rate of glucose turnover, which increases when glucagon activates hepatic glucose delivery concomitantly with insulin facilitating peripheral glucose uptake. This may be of physiologic importance after food intake, when facilitated transport of nutrients to target cells is required without an exaggerated increase in the circulating levels of the nutrients.

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