Document Detail


The role of peroxisome proliferator-activated receptor γ in pancreatic β cell function and survival: therapeutic implications for the treatment of type 2 diabetes mellitus.
MedLine Citation:
PMID:  20977574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pathogenesis of type 2 diabetes mellitus involves both peripheral insulin resistance and dysfunctional insulin secretion from the pancreatic β cell. Currently, there is intense research focus on delineating the etiologies of pancreatic β cell dysfunction in type 2 diabetes. However, there remains an unmet clinical need to establish therapeutic guidelines and strategies that emphasize the preservation of pancreatic β cell function in at-risk and affected individuals. Thiazolidinediones are orally active agents approved for use in type 2 diabetes and act as agonists of the nuclear hormone receptor PPAR-γ. These drugs improve insulin sensitivity, but there is also a growing appreciation of PPAR-γ actions within the β cell. PPAR-γ has been shown to regulate directly key β cell genes involved in glucose sensing, insulin secretion and insulin gene transcription. Further, pharmacologic PPAR-γ activation has been shown to protect against glucose-, lipid-, cytokine- and islet amyloid polypeptide (IAPP)-induced activation of numerous stress pathways. This article will review the mechanisms by which PPAR-γ activation acts to maintain β cell function and survival in type 2 diabetes mellitus and highlight some of the current controversies in this field.
Authors:
D Gupta; T Kono; C Evans-Molina
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  12     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-27     Completed Date:  2011-06-03     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  1036-47     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Affiliation:
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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MeSH Terms
Descriptor/Qualifier:
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism,  physiopathology
Female
Humans
Insulin-Secreting Cells / metabolism*
Male
PPAR gamma / metabolism*,  physiology
Practice Guidelines as Topic
Thiazolidinediones / metabolism*
Grant Support
ID/Acronym/Agency:
K08 DK080225/DK/NIDDK NIH HHS; K08 DK080225-06/DK/NIDDK NIH HHS; R03 DK 089147/DK/NIDDK NIH HHS; R03 DK089147-02/DK/NIDDK NIH HHS; T32 HL079995/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/PPAR gamma; 0/Thiazolidinediones

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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