title: Chronic cadmium exposure in rats produces pancreatic impairment and insulin resistance in multiple peripheral tissues.
abstract: Previous studies have linked cadmium exposure to disturbances in carbohydrate and lipid metabolism. In this study we investigate the effects in Wistar rats of an oral cadmium exposure in drinking water on carbohydrates, lipids and insulin release. Also, using mathematical models we studied the effect of cadmium on insulin resistance and sensitivity in liver, muscle, adipose and cardiovascular tissue. Cadmium exposure induced hyperglycemia, increased insulin release after a glucose load, and caused increases in serum triglycerides, cholesterol, LDL-C and VLDL-C, and a decrease of HDL-C. In addition, there was an accumulation of cadmium in pancreas and an increase of insulin. After exposure, HOMA-IR was increased, while the HOMA-S%, QUICKI and Matsuda-DeFronzo indexes showed decreases. A decrease of insulin sensitivity was shown in muscle and liver. Additionally, cadmium increases insulin resistance in the liver, adipose tissue and cardiovascular system. Finally, β-cell functioning was evaluated by HOMA-B% index and insulin disposition index, which were decreased, while insulin generation index increased. In conclusion, cadmium increases insulin release, induces hyperglycemia and alters lipid metabolism. These changes likely occur as a consequence of reduced sensitivity and increased insulin resistance in multiple insulin-dependent and non-dependent tissues, producing a biochemical phenotype similar to metabolic syndrome and diabetes.
authors.affiliation: Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Treviño
authors.affiliation: Stem Cell Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Waalkes
authors.affiliation: Departamento de Análisis Clínicos, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Flores Hernández
authors.affiliation: Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
authors.forename: Bertha Alicia
authors.initials: BA
authors.lastname: León-Chavez
authors.affiliation: Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Alonso
authors.affiliation: Laboratorio de Investigaciones Químico Clínicas, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico. Electronic address: eduardobrambila1@yahoo.com.mx.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Brambila
mesh_terms: D000273:Adipose Tissue / Q000503:physiopathology; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002319:Cardiovascular System / Q000503:physiopathology; D007333:Insulin Resistance; D008099:Liver / Q000503:physiopathology; D008297:Male; D009132:Muscles / Q000503:physiopathology; D010179:Pancreas / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D036401:Toxicity Tests, Chronic
chemical_list: D002104:Cadmium
keywords: Cadmium; Hyperglycemia; Hyperinsulinemia; Insulin indexes; Insulin resistance; Insulin sensitivity