Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys

Lindsey E. Nicol, Timothy D. O'Brien, Daniel A. Dumesic, Tristan Grogan, Alice F Tarantal, David H. Abbott

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Polycystic ovary syndrome (PCOS) is prevalent in reproductive-aged women and confounded by metabolic morbidities, including insulin resistance and type 2 diabetes. Although the etiology of PCOS is undefined, contribution of prenatal androgen (PA) exposure has been proposed in a rhesus monkey model as premenopausal PA female adults have PCOS-like phenotypes in addition to insulin resistance and decreased glucose tolerance. PA female infants exhibit relative hyperinsulinemia, suggesting prenatal sequelae of androgen excess on glucose metabolism and an antecedent to future metabolic disease. We assessed consequences of PA exposure on pancreatic islet morphology to identify evidence of programming on islet development. Islet counts and size were quantified and correlated with data from intravenous glucose tolerance tests (ivGTT) obtained from dams and their offspring. Average islet size was decreased in PA female infants along with corresponding increases in islet number, while islet fractional area was preserved. Infants also demonstrated an increase in both the proliferation marker Ki67 within islets and the beta to alpha cell ratio suggestive of enhanced beta cell expansion. PA adult females have reduced proportion of small islets without changes in proliferative or apoptotic markers, or in beta to alpha cell ratios. Together, these data suggest in utero androgen excess combined with mild maternal glucose intolerance alter infant and adult islet morphology, implicating deviant islet development. Marked infant, but subtle adult, morphological differences provide evidence of islet post-natal plasticity in adapting to changing physiologic demands: from insulin sensitivity and relative hypersecretion to insulin resistance and diminished insulin response to glucose in the mature PCOS-like phenotype.

Original languageEnglish (US)
Article number0106527
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 1 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Nicol, L. E., O'Brien, T. D., Dumesic, D. A., Grogan, T., Tarantal, A. F., & Abbott, D. H. (2014). Abnormal infant islet morphology precedes insulin resistance in PCOS-like monkeys. PLoS One, 9(9), [0106527]. https://doi.org/10.1371/journal.pone.0106527