Dataset Information

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

ABSTRACT:

Aims

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice.

Methods

C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice.

Results

SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation.

Conclusions

HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

SUBMITTER: Ellenbroek JH

PROVIDER: S-EPMC3575501 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

Ellenbroek Johanne H JH Töns Hendrica A HA de Graaf Natascha N Loomans Cindy J CJ Engelse Marten A MA Vrolijk Hans H Voshol Peter J PJ Rabelink Ton J TJ Carlotti Françoise F de Koning Eelco J EJ

PloS one 20130218 2

<h4>Aims</h4>Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice.<h4>Methods</h4>C57BL/6J mice were fed a HF ...[more]

PMID: 23441226

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Project description:This dataset contains proteomic data from mice with high or low weight gain in response to a high fat diet. Both host and microbial proteins are present. In the supplemental, there are also tables and supplementary files that can be used for replicating the bioinformatic analysis. Abstract: Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. While genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n=50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n=5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. While future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.

Dataset Information

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

Aims

Methods

Results

Conclusions

Publications

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

Similar Datasets

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