| Hepatic insulin gene therapy diminishes liver glycogen despite insulin responsive transcriptional effects in diabetic CD-1 mice. | |
| | |
MedLine Citation:
|
PMID: 19434628 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Hepatic insulin gene therapy (HIGT) produces near-normal glycemia in diabetic rats. Hepatic insulin production is expected to stimulate glycogen storage. However, the effect of HIGT on hepatic glycogen metabolism in vivo is unknown. METHODS: After administration of an adenoviral vector capable of inducing glucose responsive insulin production from hepatocytes, we evaluated circulating hormones, cytokines, hepatic gene expression and hepatic glycogen content in diabetic CD-1 mice receiving intravenous streptozotocin. Nondiabetic mice and diabetic mice treated with empty adenovirus served as controls. RESULTS: Peripheral concentrations of human insulin in HIGT mice were less than concentrations of mouse insulin among controls. However, expression of insulin responsive genes in HIGT livers indicated a significant intra-hepatic insulin effect, with expression changes reflecting appropriate responses to fed-fasting transitions. Transcription factors (hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor gamma co-activator-1alpha), as well as target genes (phospho-enol-pyruvate carboxykinase, glucose-6-phosphatase and glucokinase) exhibited insulin responsive expression. Despite producing near normal glycemia, HIGT diminished hepatic glycogen content in both fasted and fed mice. Serum cytokine responses revealed both vector-related (monocyte chemoatractant protein-1, interleukin-6) and transgene specific (resistin, tumor necrosis factor alpha) effects. CONCLUSIONS: HIGT produces low circulating concentrations of insulin, but produces significant intra-hepatic effects on gene expression. Despite controlling hyperglycemia, HIGT exerts unexpected insulin effects on hepatic carbohydrate metabolism. Although the precise mechanisms remain to be determined, they may relate to vector-induced cytokine effects. |
| | |
Authors:
|
Jin-an Zhang; Dingwu Jia; Darin E Olson; Adam G Campbell; Peter M Thulé |
Related Documents
:
|
1464458 - Effect of insulin on glucose and glycogen metabolism and leucine incorporation into pro... 8307248 - Metabolic origin of insulin resistance in obesity with and without type 2 (non-insulin-... 6403378 - Comparative effects of insulin and hydrocortisone on glycogen content of fetal and newb... 2121778 - Fasting hyperglycemia normalizes oxidative and nonoxidative pathways of insulin-stimula... 19068958 - Skin manifestations of diabetes. 9105558 - Plasma levels of lipid and cholesterol oxidation products and cytokines in diabetes mel... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: The journal of gene medicine Volume: 11 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2009 Jul |
Date Detail:
|
Created Date: 2009-06-24 Completed Date: 2009-08-24 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
|
Languages: eng Pagination: 588-97 Citation Subset: IM |
Copyright Information:
|
2009 John Wiley & Sons, Ltd. |
Affiliation:
|
Department of Endocrinology, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adipokines
/
metabolism Animals Body Weight Cytokines / metabolism Diabetes Mellitus, Experimental* / genetics, metabolism Disease Models, Animal Gene Expression Regulation* Gene Therapy* Humans Insulin* / genetics, metabolism, therapeutic use Liver / physiology Liver Glycogen / metabolism* Male Mice Rats Transcription, Genetic* |
| Grant Support | |
ID/Acronym/Agency:
|
DKO 7298//PHS HHS |
| Chemical | |
Reg. No./Substance:
|
0/Adipokines; 0/Cytokines; 0/Liver Glycogen; 11061-68-0/Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of positive reinforcement training techniques on the psychological welfare of zoo-housed chi...
Next Document: Captive and wild orangutan (Pongo sp.) survivorship: a comparison and the influence of management.