Open Access Theses and Dissertations

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You searched for subject:(Insulin secretion dynamics). Showing records 1 – 3 of 3 total matches.

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Georgia Tech

1. Cheng, Shing-Yi. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.

Degree: PhD, Chemical Engineering, 2005, Georgia Tech

URL: http://hdl.handle.net/1853/7160 

Genetically engineered cells have the potential to solve the cell availability problem in developing a pancreatic tissue substitute for the treatment of insulin-dependent diabetes (IDD). These cells can be beta-cells genetically engineered so that they can be grown in culture, such as the betaTC3 and betaTC tet mouse insulinomas developed by Efrat et al; or, they can be non-beta cells genetically engineered to secrete insulin constitutively or under transcriptional regulation. The aim of this work was to thoroughly characterize and improve the secretion dynamics of pancreatic substitutes based on genetically engineered cells. One issue involved with the continuous beta-cell lines is the remodeling of the cells inside an encapsulated cell system, which may affect the insulin secretion dynamics exhibited by the construct. To evaluate the effect of remodeling on the secretion properties of the construct, we used a single-pass perfusion system to characterize the insulin secretion dynamics of different alginate beads in response to step-ups and downs in glucose concentration. Results indicated that the secretion dynamics of beads indeed changed after long-term culture. On the other hand, data with a growth-regulated cell line, betaTC tet cells, showed that the secretion profile of beads can be retained if the cell growth is suppressed. A major concern associated with genetically engineered cells of non-beta origin is that they generally exhibit sub-optimal insulin secretion characteristics relative to normal pancreatic islets. Instead of relying on molecular tools such as manipulating gene elements, our approach was to introduce a glucose-responsive material acting as a control barrier for insulin release from a device containing constitutively secreting cells. Proof-of-concept experiments were performed with a disk-shaped prototype based on recombinant HepG2 hepatomas or C2C12 myoblasts, which constitutively secreted insulin, and concanavalin A (con A)-based glucose-responsive material as the control barrier. Results demonstrated that the a hybrid pancreatic substitute consisting of constitutively secreting cells and glucose-responsive material has the potential to provide a more physiologic regulation of insulin release than the cells by themselves or in an inert material. Advisors/Committee Members: Sambanis, Athanassios (Committee Chair), Chaikof, Elliot (Committee Member), Lyon, L. Andrew (Committee Member), Thule, Peter (Committee Member), Wick, Timothy (Committee Member).

Subjects/Keywords: Pancreatic substitute; Insulin secretion dynamics; Glucose-responsive; Genetically engineered cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cheng, S. (2005). Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7160

Chicago Manual of Style (16th Edition):

Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Doctoral Dissertation, Georgia Tech. Accessed April 14, 2021. http://hdl.handle.net/1853/7160.

MLA Handbook (7th Edition):

Cheng, Shing-Yi. “Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells.” 2005. Web. 14 Apr 2021.

Vancouver:

Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/1853/7160.

Council of Science Editors:

Cheng S. Development of a Tissue Engineered Pancreatic Substitute Based on Genetically Engineered Cells. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7160


University of Queensland

2. Do, Hoang Oanh. Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes.

Degree: School of Biomedical Sciences, 2016, University of Queensland

URL: http://espace.library.uq.edu.au/view/UQ:386310 

Subjects/Keywords: Type 2 diabetes; Pancreatic islets; Beta-cells; Insulin secretion; Two photon; db/db mice; Insulin granules dynamics; Progression of diabetes; Compound exocytosis; 0601 Biochemistry and Cell Biology; 0606 Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Do, H. O. (2016). Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes. (Thesis). University of Queensland. Retrieved from http://espace.library.uq.edu.au/view/UQ:386310

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Do, Hoang Oanh. “Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes.” 2016. Thesis, University of Queensland. Accessed April 14, 2021. http://espace.library.uq.edu.au/view/UQ:386310.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Do, Hoang Oanh. “Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes.” 2016. Web. 14 Apr 2021.

Vancouver:

Do HO. Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes. [Internet] [Thesis]. University of Queensland; 2016. [cited 2021 Apr 14]. Available from: http://espace.library.uq.edu.au/view/UQ:386310.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Do HO. Structural and functional changes of pancreatic beta-cells during the progression of disease in the Leprdb model of type 2 diabetes. [Thesis]. University of Queensland; 2016. Available from: http://espace.library.uq.edu.au/view/UQ:386310

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

3. Wang, Rong. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/21417 

Insulin synthesis and secretion, as well as cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in any of these aspects leads to development of diabetes. PERK (EIF2AK3) is essential for normal development and function of the insulin-secreting β-cell. Genetic ablation of PERK in humans and mice results in permanent neonatal diabetes featuring insufficient β-cell mass, impaired insulin synthesis and ablated insulin secretion. However, previous attempts to identify the primary functions of PERK were confounded by those severe abnormalities within PERK-deficient β-cells. Here, I used a newly developed and highly specific inhibitor of PERK to determine the immediate effects of acute PERK activity inhibition. Stimulated subcellular Ca2+ signaling and insulin secretion in human and rodent β-cells was found to be rapidly reduced as a consequence of acute inhibition of PERK. These PERK-dependent dysfunctions stem from alterations in store-operated Ca2+ entry, sarcoplasmic-endoplasmic reticulum Ca2+ ATPase activity, and possibly some of the transient receptor potential channels. I also found that PERK regulates calcineurin, and pharmacological inhibition of calcineurin results in similar defects on stimulus-secretion coupling. My findings by using PERK inhibitor demonstrate that PERK acutely regulates β-cell Ca2+ signaling and insulin secretion. In addition, I used an alternative strategy to identify the primary functions of PERK by examining mice with one copy of the loss-of function Perk mutation (Perk heterozygous mice). Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. I found that Perk heterozygous mice first exhibited elevated proinsulin synthesis, changes in ER chaperone expression, and enhanced insulin secretion during neonatal and juvenile development, followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These effects of Perk heterozygosity are opposite to what has been learned from previously studies using Perk knockout mice and therefore suggest an inverted U-shaped dose effect on insulin production and secretion with half-dosage (Perk heterozygotes) defining the maximum. Moreover, because commonly used sensitive markers for ER stress were not differentially expressed in Perk heterozygous mice, these PERK-dependent differences are not likely to entail the well-known function of PERK in ER stress response. Taken together my thesis work suggests that PERK has two major functions in the pancreatic β-cells: 1) acutely regulating insulin secretion through modulation of Ca2+ dynamics in a calcineurin-dependent pathway; and 2) impacting proinsulin folding and quality control in a longer-term through modulation of ER chaperone expression. These two major functions of PERK coordinate with each other and influence whole-body insulin production and glucose… Advisors/Committee Members: Douglas Cavener, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Gong Chen, Committee Member, Melissa Rolls, Committee Member.

Subjects/Keywords: PERK eIF2alpha kinase; Ca2+ dynamics; insulin secretion; insulin biosynthesis; diabetes; ER stress; beta cell proliferation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Wang, R. (2014). PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/21417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/21417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Web. 14 Apr 2021.

Vancouver:

Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/21417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/21417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.