Changes in beta cell function occur in prediabetes and early disease in the Leprdb mouse model of diabetes

Do, Oanh H., Gunton, Jenny E., Gaisano, Herbert Y. and Thorn, Peter (2016) Changes in beta cell function occur in prediabetes and early disease in the Leprdb mouse model of diabetes. Diabetologia, 59 6: 1222-1230. doi:10.1007/s00125-016-3942-3


Author Do, Oanh H.
Gunton, Jenny E.
Gaisano, Herbert Y.
Thorn, Peter
Title Changes in beta cell function occur in prediabetes and early disease in the Leprdb mouse model of diabetes
Formatted title
Changes in beta cell function occur in prediabetes and early disease in the Leprdb mouse model of diabetes
Journal name Diabetologia   Check publisher's open access policy
ISSN 1432-0428
0012-186X
Publication date 2016-06
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s00125-016-3942-3
Open Access Status DOI
Volume 59
Issue 6
Start page 1222
End page 1230
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2017
Language eng
Formatted abstract
Aims/hypothesis: Type 2 diabetes is a progressive disease that increases morbidity and the risk of premature death. Glucose dysregulation, such as elevated fasting blood glucose, is observed prior to diabetes onset. A decline in beta cell insulin secretion contributes to the later stages of diabetes, but it is not known what, if any, functional beta cell changes occur in prediabetes and early disease.

Methods: The Leprdb mouse (age 13–18 weeks) was used as a model of type 2 diabetes and a two-photon granule fusion assay was used to characterise the secretory response of pancreatic beta cells.

Results: We identified a prediabetic state in db/db mice where the animals responded normally to a glucose challenge but have elevated fasting blood glucose. Isolated islets from prediabetic animals secreted more and were bigger. Insulin secretion, normalised to insulin content, was similar to wild type but basal insulin secretion was elevated. There was increased glucose-induced granule fusion with a high prevalence of granule–granule fusion. The glucose-induced calcium response was not changed but there was altered expression of the exocytic machinery. db/db animals at the next stage of disease had overt glucose intolerance. Isolated islets from these animals had reduced insulin secretion, reduced glucose-induced granule fusion events and decreased calcium responses to glucose.

Conclusions/interpretation: Beta cell function is altered in prediabetes and there are further changes in the progression to early disease.
Keyword Beta cell
Compound exocytosis
Exocytosis
Insulin granules
Islets
Prediabetes
Progression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 03 May 2016, 00:36:29 EST by System User on behalf of Learning and Research Services (UQ Library)