Jannifer B Tyrrell1, Samar Hafida2, Paul Stemmer3, Angie Adhami1, Todd Leff4. 1. Department of Pathology and the Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48201, United States. 2. Division of Endocrinology, Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201, United States. 3. Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, United States. 4. 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.
Abstract
BACKGROUND: Pb (lead) exposure occurs at elevated frequency in urban inner city populations that also have high rates of obesity and diabetes. OBJECTIVES: 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. Copyright Â
BACKGROUND:Pb (lead) exposure occurs at elevated frequency in urban inner city populations that also have high rates of obesity and diabetes. OBJECTIVES: 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 rathepatoma 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. Copyright Â
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