Dataset Information

Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes.

ABSTRACT: Since the fundamental defect in both type 1 and type 2 diabetes is ?-cell failure, there is increasing interest in the capacity, if any, for ?-cell regeneration. Insights into typical ?-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for ?-cell regeneration as means to reverse the deficit in ?-cell mass in diabetes. We assessed the mean ?-cell age and lifespan by the classical McKendrick-von Foester equation that describes the age-based heterogeneity of ?-cells in terms of the time-varying ?-cell formation and loss estimated by a ?-cell turnover model. This modeling approach was applied to evaluate ?-cell lifespan in a rodent model of type 2 diabetes in comparison with nondiabetic controls. When rats were 10 mo old, mean ?-cell lifespan was 1 mo vs. 6 mo in rats with type 2 diabetes vs. controls. A shortened ?-cell lifespan in a rat model of type 2 diabetes results in a decrease in mean ?-cell age and thus contributes to decreased ?-cell mass.

SUBMITTER: Manesso E

PROVIDER: S-EPMC3279301 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes.

Manesso Erica E Toffolo Gianna M GM Butler Alexandra E AE Butler Peter C PC Cobelli Claudio C

American journal of physiology. Endocrinology and metabolism 20110222 5

Since the fundamental defect in both type 1 and type 2 diabetes is β-cell failure, there is increasing interest in the capacity, if any, for β-cell regeneration. Insights into typical β-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for β-cell regeneration as means to reverse the deficit in β-cell mass in diabetes. We assessed the mean β-cell age and lifespan by the classical McKendrick-von Foester eq ...[more]

PMID: 21343541

Similar Datasets

Project description:The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells.

Dataset Information

Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes.

Publications

Shortened {beta}-cell lifespan leads to {beta}-cell deficit in a rodent model of type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets