Proglucagon-Derived Peptides in the Neuroendocrine System
The proglucagon gene is expressed in a diversity of cell types, most notably the pancreatic A cell, the intestinal L cell, and selected neurons in the hypothalamus and brain stem1–3. Much interest in the pGdp’s has been generated over the past several years with the isolation and sequence analysis of both the gene and the cDNA for proglucagon4–6. Proglucagon was found not only to contain the sequences for glucagon and several large glucagon-containing peptides (glicentin and oxyntomodulin), but was also predicted to give rise by proteolytic cleavage to two glucagon-like peptides (GLP-1 and -2) (Fig. 1). Synthesis and secretion of the proglucagon-derived peptides (pGdp’s) are now known to be subject to tissue-specific regulation, at the levels of gene expression, post- translational processing and peptide secretion. For example, plasma and tissue levels of the intestinal pGdp’s rise 2- to 3-fold in streptozotocin-diabetic rats, while concentrations in the pancreas and brain are not markedly altered7. Furthermore, changes in proglucagon post-translational processing occur in the brain of the developing rat, but not in the pancreas or intestine8. In this review, I will discuss some of the work we have done to elucidate the mechanisms underlying tissue-specific differences in the production of the pGdp’s.
KeywordsPancreatic Islet Phorbol Myristate Acetate Phorbol Myristate Acetate Glucagon Gene Proglucagon Gene
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