Genetic studies of endocrine function and metabolic regulation by the corpora cardiaca cells in Drosophila melanogaster
Abstract/Contents
- Abstract
- In humans, the hormones insulin and glucagon are the principal regulators of blood sugar homeostasis. In the fruit fly, Drosophila melanogaster, the regulation of circulating sugar levels is similarly controlled by insulin-like and glucagon-like factors. Insulin signaling in Drosophila has been studied intensively; by contrast, relatively little is known about the genetic regulation of Drosophila Adipokinetic hormone (Akh), the polypeptide with glucagon-like functions, and the corpora cardiaca (CC) cells that produce Akh. Here I describe the use of an enhancer trap screen that led to the identification of a novel regulator of CC function, the homeodomain transcription factor unplugged (unpg). Knocking down unpg in the CC cells results in decreased Akh transcript levels and reduced circulating glucose and trehalose. I also describe the identification of a number of enhancer traps that are capable of driving GFP expression in the CC cells, suggesting a role for the associated genes in CC cell function. As in human diabetes, insulin deficiency in the fruit fly elevates circulating glucose levels and impairs triglyceride regulation. Reduced insulin signaling in Drosophila also increases expression of the adipokine Akh, a phenotype reminiscent of the excessive glucagon signaling that accompanies human diabetes. Thus, it remains unclear if insulin deficiency or adipokine excess is the primary basis for diabetic phenotypes in flies lacking insulin-producing cells. Here I show that simultaneous targeted ablation of cells producing Drosophila insulin and adipokinetic hormone results in hypoglycemia. Mutation of the gene encoding the Akh receptor (Akhr) reduces circulating glucose levels in adult Drosophila lacking insulin, arguing that excessive Akh signaling is the basis for hyperglycemia in insulin-deficient flies. Simultaneous attenuation of insulin and Akh synthesis also produced hypoglycemic flies. Similar approaches revealed triglyceride imbalance from insulin deficiency requires Akh. Thus adipokines like Akh, not insulin, may be the principal hormonal regulators of glucose and lipid balance in some non-mammalian animal classes and states of insulin deficiency.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bustamante, Erika Liliana |
|---|---|
| Associated with | Stanford University, Department of Developmental Biology. |
| Primary advisor | Kim, Seung K |
| Thesis advisor | Kim, Seung K |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Fuller, Margaret |
| Thesis advisor | Tsao, Philip |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Advisor | Fuller, Margaret |
| Advisor | Tsao, Philip |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Erika L. Bustamante. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Erika Liliana Bustamante
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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