Studies with GIP/Ins cells indicate secretion by gut K cells is KATP channel independent

• Published in: American journal of physiology: endocrinology and metabolism Vol. 284; no. 5; pp. E988 - 1000
• Main Authors: Wang, Song Yan, Chi, Maggie M.-Y, Li, Lin, Moley, Kelle H, Wice, Burton M
• Format: Journal Article
• Language: English
• Published: United States 01.05.2003
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphate - physiology; Animals; Calcium Channels, L-Type - physiology; Cell Line; Enteroendocrine Cells - metabolism; Gastric Inhibitory Polypeptide - metabolism; Glycolysis; Insulin - metabolism; Insulin Secretion; Mice; Potassium Channels - physiology; Potassium Channels, Inwardly Rectifying - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00398.2002

Division of Metabolism, Departments of 1  Internal Medicine and 2  Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110 K cells are a subpopulation of enteroendocrine cells that secrete glucose-dependent insulinotropic polypeptide (GIP), a hormone that promotes glucose homeostasis and obesity. Therefore, it is important to understand how GIP secretion is regulated. GIP-producing (GIP/Ins) cell lines secreted hormones in response to many GIP secretagogues except glucose. In contrast, glyceraldehyde and methyl pyruvate stimulated hormone release. Measurements of intracellular glucose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate levels, as well as glycolytic flux, in glucose-stimulated GIP/Ins cells indicated that glycolysis was not impaired. Analogous results were obtained using glucose-responsive MIN6 insulinoma cells. Citrate levels increased similarly in glucose-treated MIN6 and GIP/Ins cells. Thus pyruvate entered the tricarboxylic acid cycle. Glucose and methyl pyruvate stimulated 1.4- and 1.6-fold increases, respectively, in the ATP-to-ADP ratio in GIP/Ins cells. Glyceraldehyde profoundly reduced, rather than increased, ATP/ADP. Thus nutrient-regulated secretion is independent of the ATP-dependent potassium (K ATP ) channel. Antibody staining of mouse intestine demonstrated that enteroendocrine cells producing GIP, glucagon-like peptide-1, CCK, or somatostatin do not express detectable levels of inwardly rectifying potassium (Kir) 6.1 or Kir 6.2, indicating that release of these hormones in vivo may also be K ATP channel independent. Conversely, nearly all cells expressing chromogranin A or substance P and ~50% of the cells expressing secretin or serotonin exhibited Kir 6.2 staining. Compounds that activate calcium mobilization were potent secretagogues for GIP/Ins cells. Secretion was only partially inhibited by verapamil, suggesting that calcium mobilization from intracellular and extracellular sources, independent from K ATP channels, regulates secretion from some, but not all, subpopulations of enteroendocrine cells. K cells; glucose-dependent insulinotropic polypeptide; glucagon-like peptide-1; hormone secretion; inwardly rectifying potassium channel; ATP-dependent potassium channels; insulin