Title
Pioglitazone Does Not Improve Insulin Signaling In Mice With Gh Over-Expression
Keywords
Growth hormone; Insulin signaling; Pioglitazone; Transgenic mice
Abstract
Type 2 diabetes and obesity are very serious health problems in both developed and developing countries. An increased level of GH is known to promote insulin resistance. Transgenic (Tg) mice over-expressing bovine GH are short-living and characterized, among other traits, by hyperinsulinemia and increased insulin resistance in comparison with normal (N) mice. Pioglitazone (PIO) is a member of thethiazolidinediones-a group of insulinsensitizing drugs that are selective agonists of peroxisome proliferator-activated receptor gamma (PPARγ). The aim of the study was to analyze the effects of PIO on the insulinsignaling pathway in Tg and N mice. Plasma levels of insulin and glucose as well as hepatic levels of proteins involved in insulin signaling were analyzed by ELISA or western blot methods. Treatment with PIO decreased plasma level of glucose in N mice only. Similarly, PIO increased insulinsensitivity (expressed as the relative insulin sensitivity index; RISI) only in N mice. In the liver,PIO decreased the phosphorylation of insulin receptor substrate-1 (IRS1) at a serine residue (Ser307-pS-IRS1), which inhibits insulin action, and had a tendency to increase tyrosine phosphorylation of IRS2 (Tyr-pY-IRS2) only in N mice but did not affect either of these parameters in Tg mice. Levels of total and phosphorylated mammalian target of rapamycin were increased in Tg mice. Moreover, the levelof AKT2 was decreased by PIO in N mice only. In conclusion, the lack of improvement of insulin sensitivity in insulin-resistant Tg mice during PIO treatment indicates that chronically elevated GH levelscan inhibit the beneficial effects of PIO on insulin signaling. © 2013 Society for Endocrinology.
Publication Date
10-22-2013
Publication Title
Journal of Endocrinology
Volume
219
Issue
2
Number of Pages
109-117
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1530/JOE-13-0124
Copyright Status
Unknown
Socpus ID
84885743494 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/84885743494
STARS Citation
Gesing, Adam; Bartke, Andrzej; and Masternak, Michal M., "Pioglitazone Does Not Improve Insulin Signaling In Mice With Gh Over-Expression" (2013). Scopus Export 2010-2014. 6364.
https://stars.library.ucf.edu/scopus2010/6364