2159-P: Beta-Cell Compensation to Pubertal Insulin Resistance Is Compromised in High-Fat Fed Rats and Impairs Glucose Homeostasis Later in Life

Abstract

Background: Puberty is a time of hormonal changes that are associated with insulin resistance (IR). Although insulin sensitivity is restored at the end of puberty in healthy youth, it does not resolve in obese adolescents leading to an increased risk of metabolic disease such as type 2 diabetes. In pregnancy and obesity-induced IR, β-cells increase their functional mass to maintain glucose homeostasis. During puberty, however, the mechanism of pancreatic β-cell compensation to IR and its role in glucose metabolism later in life have not been established. Objective: To characterize pancreatic β-cell adaptation to pubertal IR in rats and study the effect of metabolic stress during puberty on glucose homeostasis in adult animals. Methods: Male and female Wistar rats were fed a chow diet or a high fat diet (HFD) during puberty. Body weight, fasted plasma insulin, glucose tolerance and hormone levels (estradiol, testosterone, insulin growth factor-1 (IGF1), growth hormone (GH)) were determined every 5 days from weaning to adulthood. β-cell proliferation was assessed by immunostaining of pancreatic cryosections for Ki67 and insulin to mark β-cells and β-cell mass by morphometric analysis of insulin staining. Results: During puberty, glucose intolerance was associated with an increase in insulin levels in both sexes, suggestive of IR. Correspondingly, β-cell proliferation increased, as did islet size and β-cell mass. β-cell expansion correlated with a rise in IGF1/GH levels. HFD during puberty impaired glucose tolerance in adults. Conclusion: During puberty in rats, β-cells compensate for increased IR. Metabolic stress during puberty impairs glucose homeostasis later in life. Future studies will address whether β-cell expansion during puberty is under control of the IGF1/GH axis. Disclosure A. Castell: None. M. Ethier: None. G. Fergusson: None. J. Ghislain: None. V. Poitout: None. Funding National Institutes of Health; Societé Francaise d'Endocrinologie Diabetologie Pediatrique