Document Detail


Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates.
MedLine Citation:
PMID:  23420316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic high caloric intake has contributed to the increased prevalence of pediatric obesity and related morbidities. Most overweight or obese children, however, do not present with frank metabolic disease but rather insulin resistance or subclinical precursors. The innate immune system plays a role in the pathophysiology of type 2 diabetes but how it contributes to early metabolic dysfunction in children on chronic high-fat diet (HFD) is unclear. We hypothesize that such inflammation is present in the pancreas of children and is associated with early insulin resistance. We used nonhuman primate (NHP) juveniles exposed to chronic HFD as a model of early pediatric metabolic disease to demonstrate increased pancreatic inflammatory markers before the onset of significant obesity or glucose dysregulation. Pancreata from 13-month-old Japanese macaques exposed to a HFD from in utero to necropsy were analyzed for expression of cytokines and islet-associated macrophages. Parameters from an intravenous glucose tolerance test were correlated with cytokine expression. Before significant glucose dysregulation, the HFD cohort had a twofold increase in interleukin 6 (IL6), associated with decreased first-phase insulin response and a sexually dimorphic (male) increase in IL1β correlating with increased fasting glucose levels. The number of islet-associated macrophages was also increased. Pancreata from juvenile NHP exposed to HFD have increased inflammatory markers and evidence of innate immune infiltration before the onset of significant obesity or glucose dysregulation. Given the parallel development of metabolic disease between humans and NHPs, these findings have strong relevance to the early metabolic disease driven by a chronic HFD in children.
Authors:
L E Nicol; W F Grant; W R Grant; S M Comstock; M L Nguyen; M S Smith; K L Grove; D L Marks
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-15
Journal Detail:
Title:  The Journal of endocrinology     Volume:  217     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-06-19     Revised Date:  2014-04-11    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  207-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose / metabolism
Diet, High-Fat / adverse effects
Disease Models, Animal
Female
Insulin Resistance / physiology*
Interleukin-1beta / blood
Interleukin-6 / blood
Islets of Langerhans / pathology*
Macaca
Macrophages / pathology*
Male
Pancreatitis / etiology,  pathology*,  physiopathology*
Sex Factors
Grant Support
ID/Acronym/Agency:
5R24DK090964/DK/NIDDK NIH HHS; K12 HD057588/HD/NICHD NIH HHS; K12HD057588/HD/NICHD NIH HHS; P51 OD011092/OD/NIH HHS; R01 HD014643/HD/NICHD NIH HHS; R24 DK090964/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Interleukin-1beta; 0/Interleukin-6
Comments/Corrections
Erratum In:
J Endocrinol. 2013 Jul;218(1):X1
Note: Grant, W R [corrected to Grant, W F]

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


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