Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates

L. E. Nicol, W. F. Grant, S. M. Comstock, M. L. Nguyen, M. S. Smith, K. L. Grove, D. L. Marks

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 IL1b 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.

Original languageEnglish (US)
Pages (from-to)207-213
Number of pages7
JournalJournal of Endocrinology
Volume217
Issue number2
DOIs
StatePublished - May 2013

Keywords

  • High-fat diet
  • Increased islet-associated macrophages
  • Insulin resistance
  • Nonhuman primate

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Nicol, L. E., Grant, W. F., Comstock, S. M., Nguyen, M. L., Smith, M. S., Grove, K. L., & Marks, D. L. (2013). Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. Journal of Endocrinology, 217(2), 207-213. https://doi.org/10.1530/JOE-12-0424