Mouse Genome Informatics
ot
    Ins2Akita/?
involves: C57BL/6NSlc
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body

adipose tissue
• whole body fat mass is reduced at 8 and 3 weeks of age, however whole body lean mass is no different from wild-type
• insulin-stimulated glucose uptake in white adipose tissue is increased more than 3-fold during hyperinsulinemic-euglycemic clamps
• insulin-stimulated glucose uptake in brown adipose tissue is reduced during hyperinsulinemic-euglycemic clamps

behavior/neurological
• daily food intake is increased twofold
• mutants are less active during a 24 hour cycle

homeostasis/metabolism
• mutants show increased energy expenditure during a 24 hour cycle
• both rate of oxygen consumption and carbon dioxide production are increased by about 40%
• both rate of oxygen consumption and carbon dioxide production are increased by about 40%
• respiratory exchange ratio is reduced, indicating increased lipid oxidation
• during hyperinsulinemic-euglycemic clamps, mutants show a 40% reduction in insulin-stimulated whole body glucose turnover
• basal hepatic glucose production is increased
• hepatic glucose production remains elevated during the insulin clamp unlike in wild-type mice which show a decrease
• during hyperinsulinemic-euglycemic clamps, insulin-stimulated whole body glycolysis and glycogen plus lipid synthesis are reduced by 40-50%
• mutants develop overnight-fasted hyperglycemia
• fed insulin levels are reduced
• nonobese mutants develop insulin resistance in skeletal muscle, liver, and brown adipose tissue, as indicated by an approximate 80% reduction in glucose infusion rate during hyperinsulinemic-euglycemic clamps
• chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes peripheral insulin action but does not normalize hepatic insulin action
• during hyperinsulinemic-euglycemic clamps, intramuscular triglyceride levels are reduced by almost 90%
• following an overnight fast and phloridzin treatment to lower plasma glucose levels, basal plasma triglyceride levels are reduced by 40%
• however, the insulin clamp has no effect on plasma triglyceride levels in mutants compared to wild-type mice in which there is a 50% reduction
• intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps

cardiovascular system
• cardiac remodeling
• left ventricular posterior wall thickness is increased
• ventricular hypertrophy
• ventricular fractional shortening and ejection fraction are altered in mutants
• chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes cardiac function

liver/biliary system
• intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps

muscle
• ventricular fractional shortening and ejection fraction are altered in mutants
• chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes cardiac function
• during hyperinsulinemic-euglycemic clamps, skeletal muscle glucose uptake is reduced by about 30%
• chronic treatment with phloridzin to chronically lower circulating glucose levels improves muscle glucose metabolism

cellular
• during hyperinsulinemic-euglycemic clamps, skeletal muscle glucose uptake is reduced by about 30%
• chronic treatment with phloridzin to chronically lower circulating glucose levels improves muscle glucose metabolism

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:130021