E-GEOD-10639 - Transcription profiling of mouse AKR/J and C57Bl/6J strain pancreatic islets from high fat fed
Submitted on 26 February 2008, released on 7 April 2008, last updated on 10 June 2011
Increased fat intake is associated with obesity and insulin resistance. In some individuals, a failure of pancreatic b-cells to increase insulin production in response to the high demands of obesity leads to diabetes. We sought to determine whether the impaired b- cell adaptation in obesity is associated with differential expression of genes involved in b-cell expansion and intermediary metabolism. Two strains of inbred mice prone to obesity, C57Bl/6J and AKR/J, were fed regular rodent chow or high-fat diet, after which islet morphology, secretory function and gene expression were assessed. AKR/J had lower blood glucose and higher insulin levels compared with C57Bl/6J mice on regular rodent chow or high fat diet. Insulin secretion was 3.2 fold higher in AKR/J than C57Bl/6J mice following intraperitoneal glucose injection. Likewise, glucose-stimulated insulin secretion from isolated islets was higher in AKR/J. Additionally, islet mass was 1.4 fold greater in AKR/J compared with C57Bl/6J. To elucidate the factors associated with the differences in insulin, we analyzed the gene expression profiles in pancreatic islets in AKR/J and C57Bl/6J mice. Of 14,000 genes examined, 220 were up-regulated and 286 were down-regulated in islets from diet-induced obese AKR/J mice compared with C57Bl/6J mice. Key genes involved in islet signaling and metabolism, e.g. glucagon like peptide-1 receptor, sterol Co-A desaturase 1 & 2 and fatty acid desaturase 2 were upregulated in obese AKR/J mice. The expression of multiple extracellular matrix proteins was also increased in AKR/J mice, suggesting a role in modulation of islet mass. Functional analyses of differentially regulated genes hold promise for elucidating factors linking obesity to alterations in islet function. Experiment Overall Design: Microarray analyses were performed on quadruplicate RNA samples of pancreatic islets from AKR and Bl6 mice placed on high-fat diet for 3 months. Pancreases from two mice were combined to yield one sample of islet RNA. All protocols were conducted as described in the Affymetrix GeneChips Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA) using 5 μg total RNA and GeneChip Mouse Expression Arrays MOE 430 (Affymetrix).
transcription profiling by array, unknown experiment type