RNAseq of the retinas of diabetic Goto-Kakizaki (GK) rats treated with spironolactone
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PROVIDER: PRJNA685424 | ENA |
REPOSITORIES: ENA
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Project description:To identify the transcriptional regulatory mechanisms associated with the biological anti-edematous and anti-inflammatory effect of spironolactone, we performed an analysis of the regulated genes in the neuroretina of GK rats aged 14 months and treated with a formulation of Spironolacton-loaded Microspheres (Sp-MSs) that released spironolactone for at least 2 months (mean size 30µm, 1µg/mg MSs/day). RNA-sequencing was performed on the neural retina and non-loade microspheres (NL-MSs) served as control treatment. The heatmaps of genes differentially regulated by Sp-MSs individuals as compared to NL-MSs showed a clear difference between the two conditions with 114 genes significantly regulated between the two groups, 27 significantly down regulated and 87 significantly up regulated (Log2FC ≥ 0,5, adjusted p<0.05). Pathway enrichment analysis using hallmark gene-set function highlighted 9 significantly regulated pathways: unfolded protein response, UV response, G2M checkpoint, allograft rejection, interferon gamma response, MTORC1 signaling, oxidative phosphorylation, MYC targets and adipogenesis (Figure EV 3B, C). Genes encoding proteins known to intervene in vascular permeability and retinal edema were counter regulated by Sp-MSs including Vldlr, Sesn2, Adcyap1, Dusp8, Pten, Slc7a1, Tjp1, Dlg1, Sema7a, although Vegf was rather up-regulated, suggested an anti-edematous mechanism independent from VEGF. The effect of Sp-MSs was confirmed by quantitative PCR for number of these genes demonstrating that spironolactone acts as a transcriptional regulator to normalize the diabetic retina.
2021-08-26 | GSE163255 | GEO
Project description:Persimmon (Diospyros kaki L. f.) is a most popular fruit in Asian countries but its peels are totally wasted despite of containing a plenty of antioxidants such as carotenoids and polyphenols. We prepared a fat-soluble extract from a persimmon peel (PP) fraction and fed type 2 diabetic Goto-Kakizaki (GK) rats with a PP extract-containing AIN-93G diet (PP diet) for 12 weeks. Compared with the control AIN-93G diet, the feeding of the PP diet reduced the plasma glutamic-pyruvate transaminase activity significantly, with accumulation of β-cryptoxanthin in the liver. A DNA microarray analysis revealed that the PP diet altered the hepatic gene expression profiles. In particular, insulin signaling pathway-related genes were significantly enriched in differentially expressed gene sets. Moreover, Western blotting analysis actually showed the promotion of IRβ tyrosine phosphorylation. All these data suggest that the PP extract administration to the GK rats improves their insulin resistance.
2011-03-17 | GSE21417 | GEO
Project description:Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. Using the Illumina RatRef-12 v1.0 array, gene expression was assessed in two insulin-target tissues (liver and adipose tissue) from seven-month-old spontaneously diabetic (Goto-Kakizaki [GK]) and non-diabetic (Brown-Norway [BN]) rats. This study was performed in parallel with miRNA expression profiling of the same rats.
2009-07-14 | GSE17059 | GEO
Project description:The Goto-Kakizak (GK) rat, a nonobese animal model of Type 2 diabetes (T2D), were developed by repeated inbreeding of glucose-intolerent individuals selected from Wistar rats. During their development, GK rats suffer from reduced beta-cell mass and insulin resistance spontaneously (T2D phenotype), which are supposed to be caused by loci holding different genotypes between GK and Wistar rats. This array CGH experiment can detect loci which show different copy numbers (genotype) between GK and Wistar rats. These loci serve as a valuable repository for mining candidates contributing to the pathogenesis of T2D.
2010-12-31 | GSE21387 | GEO
Project description:Progressive reductions in β-cell mass and function comprise the core of the pathogenesis mechanism leading to type 2 diabetes (T2D). To understand the molecular events in this process, we quantified the temporal transcriptome and proteome of pancreatic islets from Goto-Kakizaki (GK) rats at different stages of diabetes. Integrated omics analysis allowed us to unravel the chronological order of T2D-related molecular events during GK islet deterioration. Two major events occur early in the disease, specifically, a reduction in β-cell mass caused by defective neogenesis and senescence-related low proliferation, and metabolic shift caused by mitochondrial dysfunction. Furthermore, our data revealed the evolution of compensation failure in GK islets and two distinct stages of islet inflammation: priming and amplification. Our study offers a valuable resource for the diabetes research community and will facilitate further studies aimed at protecting β-cell mass and function.
2017-12-22 | GSE81811 | GEO
Project description:The genetic control of kidney and white adipose tissue transcriptomic regulation was investigated in Goto-Kakizaki (GK), Brown Norway and hybrids of an F2cross between GK and BN rats using Illumina Beadchips. Expression data was determined in 5 months old rats.
2014-01-20 | E-MTAB-969 | biostudies-arrayexpress
Project description:The Goto-Kakizak (GK) rat, a nonobese animal model of Type 2 diabetes (T2D), were developed by repeated inbreeding of glucose-intolerent individuals selected from Wistar rats. During their development, GK rats suffer from reduced beta-cell mass and insulin resistance spontaneously (T2D phenotype), which are supposed to be caused by loci holding different genotypes between GK and Wistar rats. This array CGH experiment can detect loci which show different copy numbers (genotype) between GK and Wistar rats. These loci serve as a valuable repository for mining candidates contributing to the pathogenesis of T2D. The genomic DNA taken from 3 male GK rats as 3 test samples while pooled genomic DNA from 8 male Wistar rats as the common referrence. For each of the hybridization, a dye-swap was designed as well.
2010-12-31 | E-GEOD-21387 | biostudies-arrayexpress
Project description:Persimmon (Diospyros kaki L. f.) is a most popular fruit in Asian countries but its peels are totally wasted despite of containing a plenty of antioxidants such as carotenoids and polyphenols. We prepared a fat-soluble extract from a persimmon peel (PP) fraction and fed type 2 diabetic Goto-Kakizaki (GK) rats with a PP extract-containing AIN-93G diet (PP diet) for 12 weeks. Compared with the control AIN-93G diet, the feeding of the PP diet reduced the plasma glutamic-pyruvate transaminase activity significantly, with accumulation of M-NM-2-cryptoxanthin in the liver. A DNA microarray analysis revealed that the PP diet altered the hepatic gene expression profiles. In particular, insulin signaling pathway-related genes were significantly enriched in differentially expressed gene sets. Moreover, Western blotting analysis actually showed the promotion of IRM-NM-2 tyrosine phosphorylation. All these data suggest that the PP extract administration to the GK rats improves their insulin resistance. Male GK rats (90M-bM-^@M-^S107 g), aged 5 weeks, were purchased from Japan SLC Co. (Hamamatsu, Japan). The rats were maintained in a room at 22 M-BM-1 1M-BM-0C under a 12-h light-dark cycle (lights on at 0800) and administered a commercial diet (AIN-93G, Research Diets, Inc., New Brunswick, NJ, USA) for a week. The rats were allowed free access to diet and water. After one week, they were divided into two groups with similar average body weights. The control group rats (n = 4) were fed on the commercial diet, and the PP group rats (n = 4) on the same diet containing the PP extract. After the 12-week-feeding the liver was excised and analyzed the effect of PP extract administration on hepatic gene expression.
2011-03-17 | E-GEOD-21417 | biostudies-arrayexpress
Project description:Metabolic surgery has been increasingly recommended for obese diabetic patients, but questions remain as to its effectiveness for nonobese diabetic patients and its mechanism that leads to glucose homeostasis independently of weight loss. Roux-en-Y gastric bypass (RYGB), as one of the most effective metabolic operations, excludes a portion of stomach with the proximal intestine (biliopancreatic limb, BL) and rearranges the distal end of the intestine into a Y-configuration, in which food can flow from the upper stomach pouch through the Roux limb (RL). To address the above questions to RYGB surgery, we designed a series of surgical procedures in Goto-Kakizaki （GK） rats to assess the relationship between glycemic control independent of weight loss and RL length in the RYGB procedure and studied the molecular mechanism of the RL from a systematic and comprehensive view.
2020-02-10 | GSE126835 | GEO
Project description:There has been an incresing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system we performed microarray-based gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Following pathway analysis and validation of gene lists by RT-PCR, 30 genes from hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase gamma and epsilon, ABCA1, CD47 and the RET protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipidmetabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus sriatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3diabetes. Experiments were performed with 9 animals from each group. Wistar rats (control), streptoztocin-treated Wistar rats (type 1 diabetes) and Goto-Kakizaki rats (type 2 diabetes). The brain was removed and the striatum, hippocampus and prefrontal cortex were dissected. Samples from 3-3 identically treated animals were pooled. That means, 3 biological parallels were prepared from each brain region of type 1 or type 2 diabetic and control animals, amounting to a total of 27 different pooled samples.
2011-12-15 | E-GEOD-34451 | biostudies-arrayexpress