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Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy


Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

Jens F Rehfeld. Clin Med Insights Endocrinol Diabetes.


Gastrin and cholecystokinin (CCK) are classical gastrointestinal peptide hormones. Their biogenesis, structures, and intestinal secretory patterns are well-known with the striking feature that their receptor-bound 'active sites' are highly homologous and that this structure is conserved for more than 500 million years during evolution. Consequently, gastrin and CCK are agonists for the same receptor (the CCK2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK1 receptor. The receptors are widely expressed in the body, including pancreatic islet-cell membranes. Moreover, CCK and gastrin peptides are at various developmental stages and diseases expressed in pancreatic islets; also in human islets. Accordingly, bioactive gastrin and CCK peptides stimulate islet-cell growth as well as insulin and glucagon secretion. In view of their insulinotropic effects, gastrin and CCK peptides have come into focus as drug targets, either alone or in combination with other insulinotropic gut hormones or growth factors. So far, modified CCK and gastrin peptides are being examined as potential drugs for therapy of type 1 as well as type 2 diabetes mellitus.

Keywords: Cholecystokinin (CCK); diabetes mellitus; gastrin; gastrointestinal endocrinology; peptide drugs.

Conflict of interest statement

Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


Figure 1.
Figure 1.
The C-terminal bioactive amino acid sequences of members of the gastrin/cholecystokinin family of peptides. Besides the sequences of mammalian cholecystokinin and gastrin, highly homologous sequences have been identified in extracts of frog skin glands (caerulein and phyllocaerulein) and the neural ganglion of the protochordate, Ciona intestinalis (cionin). Cionin with its disulphotyrosyl-containing sequence resembles a common ancestor candidate for gastrin and cholecystokinin.

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