Journal article
Characterization of intestinal and pancreatic dysfunction in VPAC1-null mutant mouse
Pancreas, Vol.40(6), pp.861-871
08/2011
DOI: 10.1097/MPA.0b013e318214c783
PMID: 21697765
Abstract
These studies examined the effect of homozygous deletion of vasoactive intestinal peptide receptor type 1 (VPAC1) on development and function of intestines and pancreas.
Genetically engineered VPAC1-null mutant mice were monitored for growth, development, and glucose homeostasis. Expression of VPAC1 was examined during embryonic development using VPAC1 promoter-driven β-galactosidase transgenic mice.
Homozygous deletion of VPAC1 resulted in fetal, neonatal, and postweaning death owing to failure to thrive, intestinal obstruction, and hypoglycemia. Histological findings demonstrated disorganized hyperproliferation of intestinal epithelial cells with mucus deposition and bowel wall thickening. The pancreas demonstrated small dysmorphic islets of Langerhans containing α, β, and δ cells. Expression of a VPAC1 promoter-driven transgene was observed in E12.5 and E14.5 intestinal epithelial and pancreatic endocrine cells. Vasoactive intestinal peptide receptor type 1-null mutant animals had lower baseline blood glucose levels compared to both heterozygous and wild-type littermates. Vasoactive intestinal peptide receptor type 1-deficient mice responded to oral glucose challenge with normal rise in blood glucose followed by rapid hypoglycemia and failure to restore baseline glucose levels. Insulin challenge resulted in profound hypoglycemia and inadequate glucose homeostasis in VPAC1-null mutant animals.
These observations support a role for VPAC1 during embryonic and neonatal development of intestines and endocrine pancreas.
Details
- Title: Subtitle
- Characterization of intestinal and pancreatic dysfunction in VPAC1-null mutant mouse
- Creators
- Dorit Fabricius - Department of Immunology, University of Ulm, Ulm, GermanyBahri Karacay - University of Iowa, Stead Family Department of PediatricsDamon ShuttWhitney LeverichBlanca SchaferErika TakleDaniel Thedens - University of Iowa, Electrical and Computer EngineeringGeetika KhannaSudhanshu RaikwarBaoli Yang - University of Iowa, BioVentures CenterMary E DesmondMary Sue O'Dorisio - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- Pancreas, Vol.40(6), pp.861-871
- DOI
- 10.1097/MPA.0b013e318214c783
- PMID
- 21697765
- ISSN
- 0885-3177
- eISSN
- 1536-4828
- Language
- English
- Date published
- 08/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Nursing; BioVentures Center; Obstetrics and Gynecology
- Record Identifier
- 9983557770402771
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