Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet.
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.
Moore
Gina
G
Department of Comparative Medicine, University of Washington, Seattle, WA 98195, United States. ginome68@u.washington.edu
Knoblaugh
Susan
S
Gollahon
Kathryn
K
Rabinovitch
Peter
P
Ladiges
Warren
W
D050154:Adiposity; D000821:Animal Feed; D000818:Animals; D001835:Body Weight; D003920:Diabetes Mellitus / Q000139:chemically induced*; D004032:Diet; D018149:Glucose Intolerance / Q000097:blood; D006943:Hyperglycemia / Q000097:blood; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053484:RecQ Helicases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000071657:Werner Syndrome Helicase
D020738:Leptin; D053484:RecQ Helicases; D000071657:Werner Syndrome Helicase; C499253:Wrn protein, mouse