Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet

• Published in: Mechanisms of ageing and development Vol. 129; no. 4; pp. 201 - 206
• Main Authors: Moore, Gina, Knoblaugh, Susan, Gollahon, Kathryn, Rabinovitch, Peter, Ladiges, Warren
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.04.2008; Elsevier Science
• Subjects: Adiposity; Animal Feed; Animals; Biological and medical sciences; Body Weight; Development. Metamorphosis. Moult. Ageing; Diabetes Mellitus - chemically induced; Diet; Fundamental and applied biological sciences. Psychology; Glucose Intolerance - blood; High fat and sugar diet; Hyperglycemia - blood; Hyperinsulinism - genetics; Hyperinsulinism - metabolism; Hypertriglyceridemia - blood; Insulin Resistance; Leptin - blood; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Progeriod syndrome; RecQ Helicases - deficiency; RecQ Helicases - genetics; RecQ Helicases - metabolism; Type 2 diabetes; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Werner Syndrome Helicase; Werner's syndrome; Type 2 diabetes; Obesity; Werner's syndrome; High fat and sugar diet; Progeriod syndrome; Endocrinopathy; Hyperinsulinemia; Skin disease; Senescence; Rodentia; Nutrition disorder; Metabolic diseases; Genetic disease; Feeding; Eye disease; Vertebrata; Mammalia; Diet; Mouse; Fat; Insulin resistance; Werner syndrome; Nutritional status; Sugar
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2007.12.009

Werner syndrome (WS) is an autosomal recessive progeroid syndrome caused by mutations in the Werner (Wrn) gene. WS patients have increased incidence of a number of chronic conditions including insulin resistance and type 2 diabetes. Since ingestion of foods that are high in fat and sugar is associated with increased incidence of diabetes, we examined if Wrn mutations might affect metabolic response to a diabetogenic diet. Four-month-old mice with a null mutation for the Wrn gene were fed a diet consisting of 36% fat (lard), 33% table sugar, and 20% protein plus balanced vitamins and minerals. Wrn null mice had significantly increased body weights, increased serum insulin levels, impaired glucose tolerance, and insulin resistance during 4 months of eating the diabetogenic diet. Diffuse fatty infiltration of the liver and pancreatic islet hyperplasia was characteristic morphological features. These observations suggest that Wrn null mice have impaired glucose homeostasis and fat metabolism, and may be a useful model to investigate metabolic conditions associated with aging.