Document Detail


Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic.
MedLine Citation:
PMID:  15220184     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Type 2 diabetes arises from a combination of impaired insulin action and defective pancreatic beta-cell function. Classically, the two abnormalities have been viewed as distinct yet mutually detrimental processes. The combination of impaired insulin-dependent glucose metabolism in skeletal muscle and impaired beta-cell function causes an increase of hepatic glucose production, leading to a constellation of tissue abnormalities that has been referred to as the diabetes "ruling triumvirate." Targeted mutagenesis in mice has led to a critical reappraisal of the integrated physiology of insulin action. These studies indicate that insulin resistance in skeletal muscle and adipose tissue does not necessarily lead to hyperglycemia, so long as insulin sensitivity in other tissues is preserved. Additional data suggest a direct role of insulin signaling in beta-cell function and regulation of beta-cell mass, thus raising the possibility that insulin resistance may be the overarching feature of diabetes in all target tissues. I propose that we replace the original picture of a ruling triumvirate with that of a squabbling republic in which every tissue contributes to the onset of the disease.
Authors:
Domenico Accili
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Publication Detail:
Type:  Lectures; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes     Volume:  53     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-28     Completed Date:  2004-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1633-42     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Naomi Berrie Diabetes Center, College of Physicians & Surgeons of Columbia University, Columbia University, New York, NY, USA. da230@columbia.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Division
Diabetes Mellitus, Type 2 / etiology,  genetics
Forkhead Transcription Factors
Genetic Predisposition to Disease
Glucose / metabolism
Humans
Insulin / physiology*
Insulin Resistance / genetics
Islets of Langerhans / cytology,  metabolism
Liver / physiology
Metaphor
Muscle, Skeletal / metabolism
Pancreatic Ducts / cytology
Signal Transduction
Transcription Factors / metabolism
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Transcription Factors; 11061-68-0/Insulin; 50-99-7/Glucose

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


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