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NCI-H716 Cells

Jeffrey Gagnon and Patricia L. Brubaker

Abstract The endocrine response to nutrient ingestion is vital to the maintenance of energy homeostasis in the body. Glucagon like peptide-1 (GLP-1) is one such hormone that is released from L-cells of the distal small intestine and colon in response to meal ingestion. GLP-1 acts on various systems in the body to enhance glucose-stimulated insulin secretion, delay gastric emptying and promote satiety. As such, elevating the levels of active GLP-1 in the circulation, as well as enhancing GLP-1 bioactivity, is the basis of several recent anti-diabetic medications. Gaining an understanding of how GLP-1 secretion is regulated at the cellular level requires in vitro L-cell models. NCI-H716 is a cell line derived from ascites fluid of a colorectal adenocarcinoma from a 33 year old Caucasian male. This cell line is currently the only human model available for the in vitro study of GLP-1 regulation and is the topic of the following chapter. This chapter will cover the origin, characteristics and methods for using this model. Comparisons are then made between other available in vitro GLP-1 models.

Keywords GLP-1 • Endocrine hormone • Nutrient • Neurotransmitter • Receptor • Cell line • Cell culture • L-cell • Secretion • Enteroendocrine • Human

Introduction

Glucagon like peptide 1 (GLP-1) is a key hormone in the regulation of nutrient metabolism. Its release from intestinal enteroendocrine L-cells is stimulated by the ingestion of nutrients (both directly, through luminal nutrient sensing, and indirectly, via parasympathetic innervation). The L-cells are distributed primarily in the distal small intestine and colon. Once released into the circulation, GLP-1 acts to promote satiety as well as the storage of ingested nutrients. A well-established and pharmacologically-targeted aspect of GLP-1 action is its role in potentiating glucosestimulated insulin secretion from the β cells of the pancreas. This action creates a larger insulin response to ingested glucose as compared to isoglycemic levels of glucose delivered intravenously, and is known as the incretin effect. The GLP-1 responses to various dietary nutrients and their respective intracellular mechanisms of action on the L-cell have been, and continue to be, intensively studied using in vitro GLP-1-secreting cell models. One such model is the human colonic cell line, NCI-H716. This review will describe the origin, utility and associated methods of use of this cell line in the study of GLP-1 biology.

 
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