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Expression data from the transplanted mouse islets into hyperglycemic and normoglycemic mice at 6 hours post-transplantation

ABSTRACT: insulin treatment protects islets from the initial rapid loss that is usually observed after transplantation and positively affects the outcome of islet transplantation in Akita mice. To study the molecular mechanism underlying the improved islet survival, expression profile analyses was performed to analyze the differences between the grafts transplanted into hyperglycemic and normoglycemic mice at 6 hours post-transplantation

ORGANISM(S): Mus musculus

PROVIDER: GSE55764 | GEO | 2014/04/18

SECONDARY ACCESSION(S): PRJNA240907

REPOSITORIES: GEO

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Expression data from the transplanted mouse islets into hyperglycemic and normoglycemic mice at 6 hours post-transplantation

Project description:insulin treatment protects islets from the initial rapid loss that is usually observed after transplantation and positively affects the outcome of islet transplantation in Akita mice. To study the molecular mechanism underlying the improved islet survival, expression profile analyses was performed to analyze the differences between the grafts transplanted into hyperglycemic and normoglycemic mice at 6 hours post-transplantation Cells were harvested at grafts for RNA extraction and hybridization on Affymetrix microarrays. We performed gene expression profiles of the transplanted mouse islets into hyperglycemic and normoglycemic mice at 6 hours post-transplantation

2014-04-18 | E-GEOD-55764 | biostudies-arrayexpress

Project description:From the past reports, we hypothesized that spleen is an ideal site for inducing regeneration of transplanted islets, and leading to reduce the required number of islets for ameliorating the hyperglycemia of diabetic recipients in mice. In order to confirm this hypothesis, we performed 25 islets transplantation into spleen (SP25); it was not enough number to ameliorate the hyperglycemia of recipient mice, with 100 islets transplantation into beneath the kidney capsule (KC100) to maintain recipients' blood glucose normoglycemic temporary. All recipient mice (n=11) became normoglycemic after receiving SP25 with KC100. On 240 days after transplantation, we performed nephrectomy for removing islet grafts in the kidney. After nephrectomy, 8 of 11 mice remained normoglycemic, and 3 of 11 mice' non-fasting blood glucose levels were maintained around 300 mg/dL. On 290 days after transplantation (50 days after nephrectomy), all recipient mice received splenectomy to remove islet grafts in the spleen. All mice became hyperglycemic after splenectomy, indicating that intra-splenic islet grafts maintained the blood glucose levels of diabetic recipient mice. In order to investigate the gene expression associated with islets engraftment in the spleen, microarray studies were performed in comparison of the Tlx-1 (Hox11) related gene expression profiles of Sample 1, Sample 2 and Sample 3.

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Differential regulation of cerebral metabolic genes after hyperglycemic and normoglycemic cardiac arrest

Project description:Severe cerebral ischemia caused by events such as ischemic stroke or cardiac arrest is a relatively common and life-threating condition. Those who survive frequently suffer from significant cerebral dysfunction, often with poor outcome. To date the treatment options are limited. Concomitant hyperglycemia is frequently perceived both in focal and global transient ischemia, augmenting the ischemic brain injury as revealed by experimental and clinical studies. The aim with the current study was to improve the understanding of the pathogenesis behind how concomitant hyperglycemia can augment the cerebral injury seen after cerebral ischemia. To that end we performed a global transcriptome analysis of brains from hyperglycemic and normoglycemic pigs after transient global ischemia.

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Inhibition of ERK 1/2 pathway downregulates YAP1/TAZ signaling in human cardiomyocytes exposed to hyperglycemic conditions

Project description:Hyperglycemia-mediated cardiac dysfunction is an acute initiator in the development of vascular complications, leading to cardiac fibrosis. To investigate the effects of hyperglycemia-mediated changes in cardiomyocytes, cells were cultured in-vitro under normoglycemic (5 mM or 25 mM D-glucose) and hyperglycemic (5 → 50 mM or 25 → 50 mM D-glucose) conditions, respectively. After 24-hours of hyperglycemic exposure, cells were collected for RNA-sequencing (RNA-seq) studies to further investigate the differentially expressed genes (DEG) related to inflammation and fibrosis in samples cultured under hyperglycemic-in comparison with normoglycemic-conditions. Western Blotting was done to evaluate the protein expression of YAP1/TAZ under hyperglycemia induced stress conditions, as it is known to be involved in fibrotic and vascular inflammatory-mediated conditions. RNA-seq revealed the DEG of multiple targets including matrix metalloproteinases and inflammatory mediators, whose expression was significantly altered in the 5 → 50 mM in comparison with the 25 → 50 mM condition. Western Blotting showed a significant upregulation of the protein expression of the YAP1/TAZ pathway under these conditions as well (5 → 50 mM). To further probe the relationship between the inflammatory extracellular-signal-regulated kinase (ERK 1/2) and its downstream effects on YAP1/TAZ expression we studied the effect of inhibition of the ERK 1/2 signaling cascade in the 5 → 50 mM condition. The application of an ERK 1/2 inhibitor inhibited the expression of the YAP1/TAZ protein in the 5 → 50 mM condition, and this strategy may be useful in preventing and improving hyperglycemia associated cardiovascular damage and inflammation.

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Gene expression profile at single cell level of islet cells from normoglycemic or hyperglycemic mice

Project description:The purpose of the experiment was to investigate the heterogeneity of islet cell response, especially beta-cells to hyperglycemia induced by severe insulin resistance in mice.

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Genomic profiling of type-1 adult diabetic and aged normoglycemic mice liver

Project description:Here we characterized and compared differential gene expression from diabetic and normoglycemic NOD mice and from aged and young-adults Balb/c mice. Total RNA from NOD diabetic (3 weeks with glicemia over 500mg/dl) and normoglycemic NOD mice from the same age was used. To compare the effects of aging in genomic expression, total RNA from young-adult Balb/c (9 weeks old) and middle-aged Balb/c (47 weeks old) were used.

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Successful transplantation of islets into inguinal subcutaneous white adipose tissue

Project description:Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. Here we describe a novel site for islet transplantation, the inguinal subcutaneous white adipose tissue. In this site, transplanted islets are engrafted as clusters and function to reverse diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much interest, the efficiency of islet transplantation is superior to the liver, with increased mass of transplanted β cells. Furthermore, transplanted human islets function to reverse diabetes in immunodeficient mice. Thus, this adipose tissue site may be ideal for clinical islet transplantation.

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