[Glucagon-like peptides--synthesis, biological actions and some clinical implications]

Glucagon and the glucagon-like peptides (GLPs) are derived from single proglucagon gene and exhibit an increasing number of biologically important actions. As a counter-regulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. The glucagon-like peptides GLP-1 and GLP-2 are produced in enteroendocrine L cells of the small and large intestine and secreted in a nutrient-dependent manner. GLP-1 regulates nutrient assimilation via inhibition of gastric emptying and food intake. GLP-1 controls blood glucose following nutrient absorption via stimulation of glucose-dependent insulin secretion, insulin biosynthesis, islet proliferation, and neogenesis and inhibition of glucagon secretion. Glucagon-like peptide-1 (GLP-1 is an insulinotropic hormone, GLP-1 also inhibits glucagon secretion. GLP-1 lowers blood glucose in normal subjects and in patients with type 2 diabetes. The major biological action of GLP-2 appears to be the stimulation of small-bowel hyperplasia, manifested by an increases in both villous height and small-bowel weight. A pilot study of GLP-2 administration in human subjects with short bowel syndrome demonstrated significant improvements in energy absorption, bone density, increased body weight, which correlated with increased crypt plus villus height on intestinal biopsy sections. The biological actions of two of these glucagon-related peptides, suggest that they may have therapeutic relevance for the treatment of human diseases such as diabetes, selective intestinal disorders and cardiac diseases.