Circulating levels of PIN1 and glucose metabolism in young people with obesity.

Abstract

Impaired activity of the peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) isomerase might contribute to link disturbed glucose metabolism and risk of glucose related neurotoxicity, neurodegeneration and cognitive decline. The isomerase modulates also pathways of peripheral insulin sensitivity and secretion. We aimed at investigating the levels of circulating PIN1 in adolescents with obesity and any association with their glucose metabolism. We enrolled 145 adolescents (age 12-17.8years); 67 lean controls (46.2%) and 78 (53.8%) with overweight or obesity (males n = 62, 46%). We estimated glucose and insulin in fasting condition and after a standard oral glucose tolerance test; fasting serum levels of PIN1, amyloid β-protein 42 (Aβ42), presenilin 1 (PSEN1), glucagon-like peptide 1 (GLP1) and Non Esterified Fatty Acids (NEFA). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), the β cell function (HOMA-β) and the Adipo-IR. There was no difference in PIN1 serum levels between normal weight individuals and patients with obesity. However, there was an inverse correlation between serum fasting PIN1 and glucose (r -0.183 and p = 0.027). We confirmed levels of Aβ42 and PSEN1 were higher in teens with obesity than in lean controls and their correlation with the body mass index (Aβ42: r = 0.302, p = 0.0001, PSEN1 r = 0.231, p = 0.005) and the HOMA-IR (Aβ42: r = 0.219, p = 0.009, r = 0.170, p < 0.042). There was no significant rise of circulating PIN1 levels in young individuals with obesity. Increased levels reported in the literature in adult patients are likely to occur late in the natural history of the disease with the onset of an overt impairment of glucose homeostasis.