Pancreatic β- and α-cell adaptation in response to metabolic changes

Leiden Repository

Pancreatic β- and α-cell adaptation in response to metabolic changes

Type: Doctoral Thesis
Title: Pancreatic β- and α-cell adaptation in response to metabolic changes
Author: Ellenbroek, Johanne Hendrike (Rianne)
Publisher: Department of Nephrology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2015-03-25
Keywords: Endocrinology
Diabetes mellitus
Pancreas
Beta-cell
Alpha-cell
Insulin resistance
Beta-cell adaptation
Abstract: Insulin-producing pancreatic β-cells are essential to maintain blood glucose levels within a narrow range. β-cells can adapt to an increased insulin demand by enhancing insulin secretion via increased β-cell function and/or increased β-cell mass. Inadequate β-cell adaptation leads to hyperglycemia and eventually diabetes mellitus. Therefore, it is critical to understand how the β-cell mass is regulated. We investigated β- and α-cell adaptation in response to different metabolic changes. We found that β-cell adaptation in response to insulin resistance in mice, rats, and deceased organ donors was regionally heterogeneous throughout the pancreas. We also observed that the glucagon-producing α-cell mass adapts to metabolic changes, resulting in the maintenance of the α- to β-cell ratio. Furthermore, we show that treatment of normoglycemic mice with a glucagon-like-peptide-1 receptor agonist improved β-cell function and that this is associated with a decrease in β-cell mass in order to maintain normoglycemia. In mice fed a high-fat, low-carbohydrate ketogenic diet beta-cell adaptation failed, resulting in symptoms that are associated with diabetes in humans. Finally, we developed three high-throughput culture platforms for human islets to assess β-cell function that can be used in future studies to identify novel mechanisms involved in β- and α-cell adaptation.
Description: Promotores: E.J.P. de Koning, T.J. Rabelink, Co-Promotor: F. Carlotti
With Summary in Dutch
Faculty: LUMC
Citation: Ellenbroek, J.H., 2015, Doctoral Thesis, Leiden University
ISBN: 9789461089298
Sponsor: The research presented in this thesis was supported by the Diabetes Cell Therapy Initiative consortium, the Dutch Diabetes Research Foundation, the DON foundation, the Bontius Foundation and an unrestricted research grant from Novo Nordisk.
Handle: http://hdl.handle.net/1887/32608
 

Files in this item

Description Size View
application/pdf Full Text 20.06Mb View/Open
application/pdf Cover 334.8Kb View/Open
application/pdf Title Pages_Contents 117.1Kb View/Open
application/pdf Chapter 1 1.725Mb View/Open
application/pdf Chapter 2 4.693Mb View/Open Full text at publisher site
application/pdf Chapter 3 3.561Mb View/Open
application/pdf Chapter 4 2.164Mb View/Open
application/pdf Chapter 5 2.173Mb View/Open Full text at publisher site
application/pdf Chapter 6 1.228Mb View/Open Full text at publisher site
application/pdf Chapter 7 3.420Mb View/Open
application/pdf Chapter 8 1.075Mb View/Open
application/pdf Summary in Dutch 144Kb View/Open
application/pdf Curriculum Vitae_Publications 117.4Kb View/Open
application/pdf Propositions 88.05Kb View/Open

This item appears in the following Collection(s)