title: Lead (Pb) exposure promotes diabetes in obese rodents.
abstract: BACKGROUND
  Pb (lead) exposure occurs at elevated frequency in urban inner city populations that also have high rates of obesity and diabetes.
  
  
  OBJECTIVE
  To determine if Pb can promote the development of diabetes in a setting of obesity, we examined the effect of Pb exposure on glucose metabolism in a rodent model of obesity.
  
  
  METHODS
  Adult female ZDF rats were exposed to Pb in drinking water for 24 weeks. Fasting blood glucose, insulin, and glucose tolerance were measured at regular intervals. Expression of hepatic gluconeogenic genes was measured in exposed and control animals and in cultured hepatoma cells treated with Pb.
  
  
  RESULTS
  Pb exposure induced fasting hyperglycemia after 8 weeks and glucose intolerance after 12 weeks of exposure. In addition, Pb-exposed animals showed elevated hepatic triglyceride levels and increased expression of the gluconeogenic genes PEPCK and glucose-6-phosphatase. In cultured rat hepatoma cells treatment with Pb stimulated PEPCK and glucose-6-phosphatase gene expression, suggesting a possible direct effect of Pb on hepatic gluconeogenic gene expression.
  
  
  CONCLUSIONS
  In the setting of obesity, Pb exposure is prodiabetic, causing fasting hyperglycemia and glucose intolerance in rats. A contributing factor to the metabolic effects of Pb may be the direct stimulation of hepatic gluconeogenic gene expression.
authors.affiliation: Department of Pathology and the Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, United States.
authors.forename: Jannifer B
authors.initials: JB
authors.lastname: Tyrrell
authors.affiliation: Division of Endocrinology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, United States.
authors.forename: Samar
authors.initials: S
authors.lastname: Hafida
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Stemmer
authors.affiliation: Department of Pathology and the Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, United States.
authors.forename: Angie
authors.initials: A
authors.lastname: Adhami
authors.affiliation: Department of Pathology and the Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, United States. Electronic address: tleff@wayne.edu.
authors.forename: Todd
authors.initials: T
authors.lastname: Leff
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000150:complications*; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced / Q000150:complications; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D009765:Obesity / Q000150:complications*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D007854:Lead
keywords: Diabetes; Gluconeogenesis; Lead (Pb); Obesity; Rats