title: The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.
abstract: Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.
authors.affiliation: Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.affiliation: Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, Wisconsin; and.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Neuman
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Allison L
authors.initials: AL
authors.lastname: Brill
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Harpreet K
authors.initials: HK
authors.lastname: Brar
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Mary F
authors.initials: MF
authors.lastname: Thompson
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Mark T
authors.initials: MT
authors.lastname: Cadena
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Connors
authors.affiliation: Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Busch
authors.affiliation: Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Candace M
authors.initials: CM
authors.lastname: Cham
authors.affiliation: Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, Wisconsin; and.
authors.forename: Elaina K
authors.initials: EK
authors.lastname: Jones
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Carly R
authors.initials: CR
authors.lastname: Kibbe
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, Wisconsin; and.
authors.forename: Dawn B
authors.identifier: http://orcid.org/0000-0002-0239-4715
authors.initials: DB
authors.lastname: Davis
authors.affiliation: Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, Wisconsin; and.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Groblewski
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin;
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
authors.affiliation: William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin; Division of Endocrinology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin; Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison College of Agriculture and Life Sciences, Madison, Wisconsin; and mkimple@medicine.wisc.edu.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Kimple
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005526:Food, Formulated; D019886:Gastrin-Releasing Peptide / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000097:blood; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000187:drug effects*; D008049:Lipase / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D046790:Pancreas, Exocrine / Q000033:anatomy & histology / Q000187:drug effects*; D010187:Pancreatic Hormones / Q000378:metabolism; D010288:Parenteral Nutrition / Q000009:adverse effects*
chemical_list: D010187:Pancreatic Hormones; D019886:Gastrin-Releasing Peptide; D004247:DNA; D008049:Lipase; D000681:Amylases; D001839:Bombesin
keywords: adjuvant therapy; bombesin; gut hormones; pancreas; parenteral nutrition