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Physiologic Mechanisms of Insulin Resistance During a Critical Postnatal Window of Development
Author(s) -
Ortiz Rosa Isela,
ChávezMaldonado Juan Pablo,
Velasco Myrian,
Larqué Carlos Alfonso,
Hiriart Marcia
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1014.7
Subject(s) - medicine , endocrinology , insulin resistance , insulin , hyperinsulinemia , adipose tissue , insulin tolerance test , glucose tolerance test , weaning , white adipose tissue , biology , insulin sensitivity
Introduction Insulin resistance is a condition in which the insulin‐sensitive tissues cannot respond appropriately to hormone effects. Insulin resistance has been associated with pathologies however, insulin resistance is present in physiologic states such as pregnancy and adolescence. Our work group analyzed changes on glucose and insulin levels during postnatal development. We found that males and females rats near the end of lactation show insulin resistance, characterized by hyperglycemia and hyperinsulinemia, which disappears later. This state associates with a critical window in pancreatic development. Objective To determine the mechanisms involved in the insulin resistance observed in the weaning period in males and females rats. Methods We used male and female Wistar rats at 20 postnatal days (20 pd) and healthy adult rats (250–280 g). We analyzed fasting glucose and insulin levels and made glucose tolerance test (GTT) and insulin sensitivity test (ITT). We performed insulin‐stimulated glucose uptake assays in adipose tissue and analyzed P70S6K‐specific inhibitory sites of serine and threonine phosphorylation of IRS‐1 in adipose tissue and skeletal muscle. Results We observed increased fasting glucose concentrations and insulin levels in both female and male at 20 pd, compared to adult rats. The blood glucose levels in GTT in male and female rats of 20 pd were higher to those of adults, along with the test. Systemic insulin response was less in male and female at 20 pd rats, compared to adults. Insulin‐stimulated glucose uptake in adipose tissue was lower in 20 pd, compared to adults. P70S6K phosphorylation in Thr389 and IRS‐1 phosphorylation in Ser1101 were higher in adipose tissue at 20 pd in males and females rats than in adult rats. Conclusion Wistar males and females rats at 20 pd have high plasma levels of glucose and insulin compared with adult rats. These data together with the lack of response in the ITT, a higher phosphorylation of P70S6K kinase and IRS1 at a inhibitory sites and lower insulin‐stimulated glucose uptake could be involved in the development of physiological insulin resistance. Support or Funding Information This work was partially financed by CONACYT CB‐253222 and DGAPA IN213114