ETD RECORD
Novel discoveries of insulin gene regulatory mechanisms in the teleost model zebrafish :a species expressing two insulin genes
Citation
Papasani, Madhusudhan Reddy.. (2008). Novel discoveries of insulin gene regulatory mechanisms in the teleost model zebrafish :a species expressing two insulin genes. Theses and Dissertations Collection, University of Idaho Library Digital Collections. https://www.lib.uidaho.edu/digital/etd/items/etd_337.html
- Title:
- Novel discoveries of insulin gene regulatory mechanisms in the teleost model zebrafish :a species expressing two insulin genes
- Author:
- Papasani, Madhusudhan Reddy.
- Date:
- 2008
- Keywords:
- Zebra danio--Genetics Insulin--Biotechnology
- Program:
- Animal Physiology
- Abstract:
- The zebrafish has duplicated insulin genes that presumably resulted from fish-specific genome duplication event. The discovery of a second insulin gene (insb) and interesting gene expression patterns of two insulin genes (insa and insb) in zebrafish are beginning to provide novel insights into insulin functions. In developing zebrafish, insa was present as a low copy gene prior to pancreas formation, and was greatly induced after pancreas formation, whereas insb was abundant in prepanceatic stages. insa expression was observed in the developing pancreas, whereas insb was expressed in the pancreas, the blastomeres and the head. insb expression in the blastomeres and head suggests that insb may be acting as a survival and neurotrophic factor during development. Pancreatic insa and insb may both be involved in regulation of glucose homeostasis. Analyses in adult tissues suggested insa was predominantly expressed in the pancreas and also at low levels in the brain and ovaries. insb was predominantly expressed in ovaries followed by pancreas and brain. The presence insulin genes in brain and ovary suggests the other functions of insulin system such as neurotrophic actions and oogenesis in addition to glucose homeostasis. These expression patterns suggested the importance of understanding the regulatory mechanisms of the two insulin genes. In silico analyses suggested that one of the most important fundamental transcription factors, pancreatic duodenal homeobox-1 (PDX-1) has potential binding sites on both insulin gene promoters. Further analysis of pdx-1 expression patterns in embryonic development and also in adult tissues suggested its co-expression and co-localization with the duplicated insulin genes. In the present studies, the insb promoter region was determined by deletion series mutational analyses. In vitro analyses using an overexpression strategy and site directed mutagenesis of putative binding sites of PDX-1 demonstrated that PDX-1 was able to activate the insb promoter. On the other hand, a glucose dose-response study suggested that supraphysiological exposure of glucose had a repressive effect on insb promoter activity that was reversed by transient exposure to physiological doses of glucose or no glucose similar to observations of mammalian insulin promoter activity.
- Description:
- Thesis (Ph. D., Animal Physiology)--University of Idaho, May 2008.
- Major Professor:
- Rodnay A. Hill.
- Defense Date:
- May 2008.
- Type:
- Text
- Format Original:
- xiv, 155 leaves :ill. (some col.) ;29 cm.
- Format:
- record
Rights
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- In Copyright - Educational Use Permitted. For more information, please contact University of Idaho Library Special Collections and Archives Department at libspec@uidaho.edu.
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