Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

Abstract

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 CCK 2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK 1 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.

Benefits of Sustained Upregulated Unimolecular GLP-1 and CCK Receptor Signalling in Obesity-Diabetes

“…This observation fits well with reported glucagonostatic effects of GLP-1 receptor activation (45). However, it does contrast somewhat with the reported direct glucagonotropic actions of CCK (8), and detailed study of the overall impact of activation of GLP-1 and CCK1 receptors by [Lys 12 Pal]Ex-4/CCK in this regard is required.…”

“…Cholecystokinin (CCK) is a hormone primarily secreted from gastrointestinal I-cells as well as neurons of the enteric and central nervous systems (8). The peptide circulates in various molecular forms, with the octapeptide CCK-8 being the smallest form to exhibit full biological activity (9).…”

“…The peptide circulates in various molecular forms, with the octapeptide CCK-8 being the smallest form to exhibit full biological activity (9). To impart its physiological actions, CCK binds and activates specific receptors, namely CCK1 and CCK2, that modulate various physiological processes including satiety, pancreatic endocrine, and exocrine function as well as gastric acid and bile secretion (8). In particular, CCK-based regulation of energy intake and pancreatic endocrine islet function make the hormone a potentially attractive therapeutic agent for obesity and diabetes (9).…”

Effect of Dexmedetomidine-Assisted Intravenous Anesthesia on Gastrointestinal Motility in Colon Cancer Patients After Open Colectomy

“…Besides, GAS, MTL, and CCK are all important gastrointestinal hormones. GAS can promote gastric emptying through stimulating gastric acid secretion, MTL can enhance gastrointestinal motility, and CCK can suppress gastric emptying by inhibiting the contraction of the esophageal sphincter (20). In this Study, the observation group had higher levels of GAS and MTL but had a lower level of CCK than the control group after the operation, demonstrating that Dex can regulate the levels of gastrointestinal hormones in patients with CC after open colectomy, thereby improving the gastrointestinal function.…”

Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis

“…However, there is much more to discover concerning the biology of gastrin than is indicated. A study has shown that gastrin stimulated islet-cell growth and insulin secretion, which is proposed as a potential drug therapy for diabetes mellitus (Rehfeld 2019 ). Besides, gastrin plays an essential role in maintaining normal blood pressure (Chen et al 2013 ) and protecting the kidney function against hypertensive injury (Gu et al 2021 ).…”