Intra-islet GLP-1, but not CCK, is necessary for β-cell function in mouse and human islets

Year: 2020

Type: article

Abstract: Glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are gut-derived peptide hormones known to play important roles in the regulation of gastrointestinal motility and secretion, appetite, and food intake. We have previously demonstrated that both GLP-1 and CCK are produced in the endocrine pancreas of obese mice. Interestingly, while GLP-1 is well known to stimulate insulin secretion by the pancreatic β-cells, direct evidence of CCK promoting insulin release in human islets remains to be determined. Here, we tested whether islet-derived GLP-1 or CCK is necessary for the full stimulation of insulin secretion. We confirm that mouse pancreatic islets secrete GLP-1 and CCK, but only GLP-1 acts locally within the islet to promote insulin release ex vivo. GLP-1 is exclusively produced in approximately 50% of α-cells in lean mouse islets and 70% of α-cells in human islets, suggesting a paracrine α to β-cell signaling through the β-cell GLP-1 receptor. Additionally, we provide evidence that islet CCK expression is regulated by glucose, but its receptor signaling is not required during glucose-stimulated insulin secretion (GSIS). We also see no increase in GSIS in response to CCK peptides. Importantly, all these findings were confirmed in islets from non-diabetic human donors. In summary, our data suggest no direct role for CCK in stimulating insulin secretion and highlight the critical role of intra-islet GLP-1 signaling in the regulation of human β-cell function.

Source: Scientific Reports

DOI: 10.1038/s41598-020-59799-2

Authors: Arnaldo Henrique de Souza, Jiayin Tang, Amanjot Kaur Yadev, Samuel T. Saghafi, Carly R. Kibbe, Amelia K. Linnemann, Matthew J. Merrins, Dawn Belt Davis

Institutions: University of Wisconsin–Madison, University of Wisconsin–Green Bay, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, William S. Middleton Memorial Veterans Hospital

Language: English

Topic: Pancreatic function and diabetes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,870

Funders: U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, University of Wisconsin-Madison, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases

OpenAlex ID: W3007985497