Forskning ved Københavns Universitet - Københavns Universitet

Forside

In vivo genetic screening for therapeutic targets for type 2 diabetes: Modeling insulin resistance in Drosophila

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

Standard

In vivo genetic screening for therapeutic targets for type 2 diabetes : Modeling insulin resistance in Drosophila. / Jørgensen, Anne Færch.

Department of Biology, Faculty of Science, University of Copenhagen, 2019.

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

Harvard

Jørgensen, AF 2019, In vivo genetic screening for therapeutic targets for type 2 diabetes: Modeling insulin resistance in Drosophila. Department of Biology, Faculty of Science, University of Copenhagen.

APA

Jørgensen, A. F. (2019). In vivo genetic screening for therapeutic targets for type 2 diabetes: Modeling insulin resistance in Drosophila. Department of Biology, Faculty of Science, University of Copenhagen.

Vancouver

Jørgensen AF. In vivo genetic screening for therapeutic targets for type 2 diabetes: Modeling insulin resistance in Drosophila. Department of Biology, Faculty of Science, University of Copenhagen, 2019.

Author

Jørgensen, Anne Færch. / In vivo genetic screening for therapeutic targets for type 2 diabetes : Modeling insulin resistance in Drosophila. Department of Biology, Faculty of Science, University of Copenhagen, 2019.

Bibtex

@phdthesis{a5c43055db4c4f9fb810ff9ed1a23bb9,
title = "In vivo genetic screening for therapeutic targets for type 2 diabetes: Modeling insulin resistance in Drosophila",
abstract = "Diabetes afflicts 1 in 11 adults globally and causes enormous human and economic losses. Between a fifth and half of the cost related to diabetes treatment is spent on diabetes complications, caused by suboptimal blood glucose management, suggesting that the current treatment is not adequate. In this thesis I argue that in vivo forward genetic screening in the model organism Drosophila melanogaster, may contribute to the search for new therapeutic targets for type 2 diabetes. I review commonalities between the highly conserved insulin signaling pathway and the responses to hypercaloric diets, which can cause insulin resistance through induction of intracellular stress responses and the innate immune response in both mammals and flies. In addition, I attach two manuscripts which identify two possibly conserved mechanisms of attenuation of insulin signaling, through in vivo forward genetic screening. In Manuscript I, hypoxia is found to be a key regulatory inhibitor of systemic growth. Specifically, hypoxia in the adipose tissue inhibits Drosophila insulin-like peptide (Dilp) secretion in a Hypoxia Inducible Factor a dependent manner. In Manuscript II, gut-derived Bursicon signaling is found to inhibit high sugar diet (HSD)-induced lipid accumulation, and attenuate HSD-induced Dilp expression and release via Rk in the insulin producing cells. Interestingly, while HSD-induced Bursicon inhibits Dilp expression, Bursicon signaling is necessary for expression of Dilp3. I conclude that modeling insulin signaling in Drosophila, may further our understanding of the conserved mechanisms underlying diet-induced insulin resistance, and thus may prove helpful in the search for new therapeutic targets for type 2 diabetes.",
author = "J{\o}rgensen, {Anne F{\ae}rch}",
year = "2019",
language = "English",
publisher = "Department of Biology, Faculty of Science, University of Copenhagen",

}

RIS

TY - BOOK

T1 - In vivo genetic screening for therapeutic targets for type 2 diabetes

T2 - Modeling insulin resistance in Drosophila

AU - Jørgensen, Anne Færch

PY - 2019

Y1 - 2019

N2 - Diabetes afflicts 1 in 11 adults globally and causes enormous human and economic losses. Between a fifth and half of the cost related to diabetes treatment is spent on diabetes complications, caused by suboptimal blood glucose management, suggesting that the current treatment is not adequate. In this thesis I argue that in vivo forward genetic screening in the model organism Drosophila melanogaster, may contribute to the search for new therapeutic targets for type 2 diabetes. I review commonalities between the highly conserved insulin signaling pathway and the responses to hypercaloric diets, which can cause insulin resistance through induction of intracellular stress responses and the innate immune response in both mammals and flies. In addition, I attach two manuscripts which identify two possibly conserved mechanisms of attenuation of insulin signaling, through in vivo forward genetic screening. In Manuscript I, hypoxia is found to be a key regulatory inhibitor of systemic growth. Specifically, hypoxia in the adipose tissue inhibits Drosophila insulin-like peptide (Dilp) secretion in a Hypoxia Inducible Factor a dependent manner. In Manuscript II, gut-derived Bursicon signaling is found to inhibit high sugar diet (HSD)-induced lipid accumulation, and attenuate HSD-induced Dilp expression and release via Rk in the insulin producing cells. Interestingly, while HSD-induced Bursicon inhibits Dilp expression, Bursicon signaling is necessary for expression of Dilp3. I conclude that modeling insulin signaling in Drosophila, may further our understanding of the conserved mechanisms underlying diet-induced insulin resistance, and thus may prove helpful in the search for new therapeutic targets for type 2 diabetes.

AB - Diabetes afflicts 1 in 11 adults globally and causes enormous human and economic losses. Between a fifth and half of the cost related to diabetes treatment is spent on diabetes complications, caused by suboptimal blood glucose management, suggesting that the current treatment is not adequate. In this thesis I argue that in vivo forward genetic screening in the model organism Drosophila melanogaster, may contribute to the search for new therapeutic targets for type 2 diabetes. I review commonalities between the highly conserved insulin signaling pathway and the responses to hypercaloric diets, which can cause insulin resistance through induction of intracellular stress responses and the innate immune response in both mammals and flies. In addition, I attach two manuscripts which identify two possibly conserved mechanisms of attenuation of insulin signaling, through in vivo forward genetic screening. In Manuscript I, hypoxia is found to be a key regulatory inhibitor of systemic growth. Specifically, hypoxia in the adipose tissue inhibits Drosophila insulin-like peptide (Dilp) secretion in a Hypoxia Inducible Factor a dependent manner. In Manuscript II, gut-derived Bursicon signaling is found to inhibit high sugar diet (HSD)-induced lipid accumulation, and attenuate HSD-induced Dilp expression and release via Rk in the insulin producing cells. Interestingly, while HSD-induced Bursicon inhibits Dilp expression, Bursicon signaling is necessary for expression of Dilp3. I conclude that modeling insulin signaling in Drosophila, may further our understanding of the conserved mechanisms underlying diet-induced insulin resistance, and thus may prove helpful in the search for new therapeutic targets for type 2 diabetes.

M3 - Ph.D. thesis

BT - In vivo genetic screening for therapeutic targets for type 2 diabetes

PB - Department of Biology, Faculty of Science, University of Copenhagen

ER -

ID: 236713847