Changes in the Expression of Insulin Pathway, Neutrophil Elastase and Alpha 1 Antitrypsin Genes from Leukocytes of Young Individuals with Insulin Resistance

Abstract

Walter David Cruz-Pineda,1 Olga Lilia Garibay-Cerdenares,2,3 Hugo Alberto Rodríguez-Ruíz,1,3 Inés Matia-García,1 Linda Anahí Marino-Ortega,1 Mónica Espinoza-Rojo,4 Zyanya Reyes-Castillo,5 Natividad Castro-Alarcón,6 Eduardo Castañeda-Saucedo,7 Berenice Illades-Aguiar,3 Isela Parra-Rojas1 1Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 2CONACyT-Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 3Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 4Laboratorio de Biología Molecular y Genómica, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 5Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México; 6Laboratorio de Investigación en Microbiología, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México; 7Laboratorio de Investigación en Biología Celular del Cáncer, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, MéxicoCorrespondence: Isela Parra-Rojas, Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, CP 39090, México, Tel/Fax [phone], Email [email protected] Olga Lilia Garibay-Cerdenares, CONACyT-Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, CP 39090, México, Tel/Fax [phone], Email [email protected]: Chronic hyperinsulinemia is a hallmark of insulin resistance that affects a diversity of cells, including leukocytes modifying the expression of some genes involved in insulin signaling.Purpose: The aim of this study was to evaluate how hyperinsulinemia affects the expression of genes involved in the proximal insulin signaling pathway in leukocytes from 45 young individuals grouped: normal weight with not insulin resistance (NIR), with insulin resistance (IR) and with obesity (OB-IR).Methods: qPCR was performed to analyze the expression of insulin receptor (INSR), insulin receptor substrate 1 and 2 (IRS-1 and IRS-2), neutrophil elastase (NE), alpha 1 antitrypsin (A1AT), glucose transporters 1, 3 and 4 (GLUT-1, GLUT-3 and GLUT-4) by the 2−ΔCt method, and the correlation between the genes was determined by Spearman’s test.Results: The mRNA expression analysis of all genes between NIR and IR individuals revealed no differences. However, when comparing NIR and IR individuals with OB-IR, an increase in NE and A1AT expression and a clear trend towards a decrease in IRS-2 expression was observed, whereas the comparison of IR and OB-IR showed a decrease in GLUT-3 expression. Overall, the correlation analysis showed that in the IR group there was a positive correlation only between NE with IRS-1 (r = 0.72, p = 0.003), while in the OB-IR group, there was a positive correlation between the NE and A1AT with INSR (r = 0.62, p = 0.01 and r = 0.74, p = 0.002, respectively) and with IRS-2 (r = 0.74, p = 0.002 and r = 0.76, p = 0.001, respectively).Conclusion: These results suggest that hyperinsulinemia and obesity are associated with changes in the expression of genes in leukocytes involved in the insulin pathway that are related to NE and A1AT.Keywords: insulin resistance, obesity, insulin signaling, leukocytes, neutrophil elastase, alpha 1 antitrypsin

Keywords

• insulin resistance
• obesity
• insulin signaling
• leukocytes
• neutrophil elastase
• alpha 1 antitrypsin.