Search Results
You are looking at 1 - 2 of 2 items for
- Author: Debra C DuBois x
- Refine by access: All content x
Search for other papers by Richard R Almon in
Google Scholar
PubMed
Search for other papers by Debra C DuBois in
Google Scholar
PubMed
Search for other papers by Jin Y Jin in
Google Scholar
PubMed
Search for other papers by William J Jusko in
Google Scholar
PubMed
Elevated systemic levels of glucocorticoids are causally related to peripheral insulin resistance. The pharmacological use of synthetic glucocorticoids (corticosteroids) often results in insulin resistance/type II diabetes. Skeletal muscle is responsible for close to 80% of the insulin-induced systemic disposal of glucose and is a major target for glucocorticoid-induced insulin resistance. We used Affymetrix gene chips to profile the dynamic changes in mRNA expression in rat skeletal muscle in response to a single bolus dose of the synthetic glucocorticoid methyl-prednisolone. Temporal expression profiles (analyzed on individual chips) were obtained from tissues of 48 drug-treated animals encompassing 16 time points over 72 h following drug administration along with four vehicle-treated controls. Data mining identified 653 regulated probe sets out of 8799 present on the chip. Of these 653 probe sets we identified 29, which represented 22 gene transcripts, that were associated with the development of insulin resistance. These 29 probe sets were regulated in three fundamental temporal patterns. 16 probe sets coding for 12 different genes had a profile of enhanced expression. 10 probe sets coding for eight different genes showed decreased expression and three probe sets coding for two genes showed biphasic temporal signatures. These transcripts were grouped into four general functional categories: signal transduction, transcription regulation, carbohydrate/fat metabolism, and regulation of blood flow to the muscle. The results demonstrate the polygenic nature of transcriptional changes associated with insulin resistance that can provide a temporal scaffolding for translational and post-translational data as they become available.
Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Departments of
Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Departments of
Search for other papers by Richard R Almon in
Google Scholar
PubMed
Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Departments of
Search for other papers by Debra C DuBois in
Google Scholar
PubMed
Search for other papers by William Lai in
Google Scholar
PubMed
Search for other papers by Bai Xue in
Google Scholar
PubMed
Search for other papers by Jing Nie in
Google Scholar
PubMed
Pharmaceutical Sciences, New York State Center of Excellence in Bioinformatics and Life Sciences, Departments of
Search for other papers by William J Jusko in
Google Scholar
PubMed
Progression of diabetes was studied in male Goto-Kakizaki (GK) spontaneously diabetic rats between 4 and 20 weeks of age, and compared with Wistar-Kyoto (WKY) controls. Five animals from each strain were killed at 4, 8, 12, 16, and 20 weeks of age. Body weight, plasma glucose, and plasma insulin were measured. WKY rats showed a significantly larger weight gain than GK animals from 8 weeks of age onward. Plasma glucose was relatively stable in WKY. By contrast, plasma glucose was higher in GK than WKY even at 4 weeks and continued to increase up to 12 weeks and then maintained a hyperglycemic plateau throughout the remainder of the experiment. Plasma insulin was relatively stable in WKY from 8 weeks onward but was sharply elevated in GK between 4 and 8 weeks. After 8 weeks, insulin declined in GK with GK concentrations lower than WKY at 20 weeks, suggesting β-cell failure. Gene expression in liver was explored using Affymetrix 230-2 gene arrays. Data mining identified 395 probe sets out of more than 31 000 that were differentially regulated. Excluding unidentifiable probe sets and considering duplicate probe sets, there were 311 genes that were expressed differently in the liver of the two strains. A functional analysis of these genes indicated that disruption of lipid metabolism in the liver is a major consequence of the chronic hyperglycemia in the GK strain. In addition, the results suggest that chronic inflammation contributes significantly to the development of diabetes in the GK rats.