Phenotypes Associated with This Genotype

Genotype
MGI:5504442

• Allelic Composition: Ins2^Akita/?
• Genetic Background: involves: C57BL/6NSlc

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

decreased body fat mass ( J:130021 )

♂ • whole body fat mass is reduced at 8 and 3 weeks of age, however whole body lean mass is no different from wild-type

heart left ventricle hypertrophy ( J:130021 )

♂ • ventricular hypertrophy

decreased body weight ( J:130021 )

♂

adipose tissue

decreased body fat mass ( J:130021 )

♂ • whole body fat mass is reduced at 8 and 3 weeks of age, however whole body lean mass is no different from wild-type

decreased adipocyte glucose uptake ( J:130021 )

♂ • insulin-stimulated glucose uptake in brown adipose tissue is reduced during hyperinsulinemic-euglycemic clamps

increased adipocyte glucose uptake ( J:130021 )

♂ • insulin-stimulated glucose uptake in white adipose tissue is increased more than 3-fold during hyperinsulinemic-euglycemic clamps

behavior/neurological

increased food intake ( J:130021 )

♂ • daily food intake is increased twofold

decreased locomotor activity ( J:130021 )

♂ • mutants are less active during a 24 hour cycle

homeostasis/metabolism

decreased circulating triglyceride level ( J:130021 )

♂ • 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

increased energy expenditure ( J:130021 )

♂ • mutants show increased energy expenditure during a 24 hour cycle

increased carbon dioxide production ( J:130021 )

♂ • both rate of oxygen consumption and carbon dioxide production are increased by about 40%

increased oxygen consumption ( J:130021 )

♂ • both rate of oxygen consumption and carbon dioxide production are increased by about 40%

decreased respiratory quotient ( J:130021 )

♂ • respiratory exchange ratio is reduced, indicating increased lipid oxidation

abnormal glucose homeostasis ( J:130021 )

♂ • 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%

hyperglycemia ( J:130021 )

♂ • mutants develop overnight-fasted hyperglycemia

decreased circulating insulin level ( J:130021 )

♂ • fed insulin levels are reduced

insulin resistance ( J:130021 )

♂ • 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

decreased liver triglyceride level ( J:130021 )

♂ • intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps

decreased skeletal muscle triglyceride level ( J:130021 )

♂ • during hyperinsulinemic-euglycemic clamps, intramuscular triglyceride levels are reduced by almost 90%

cardiovascular system

abnormal heart morphology ( J:130021 )

♂ • cardiac remodeling

thick interventricular septum ( J:130021 )

♂

abnormal heart left ventricle morphology ( J:130021 )

♂ • left ventricular posterior wall thickness is increased

heart left ventricle hypertrophy ( J:130021 )

♂ • ventricular hypertrophy

abnormal cardiac muscle contractility ( J:130021 )

♂ • 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

decreased liver triglyceride level ( J:130021 )

♂ • intrahepatic triglyceride levels are reduced during hyperinsulinemic-euglycemic clamps

muscle

heart left ventricle hypertrophy ( J:130021 )

♂ • ventricular hypertrophy

abnormal cardiac muscle contractility ( J:130021 )

♂ • ventricular fractional shortening and ejection fraction are altered in mutants

♂ • chronic treatment with phloridzin to chronically lower circulating glucose levels normalizes cardiac function

decreased muscle cell glucose uptake ( J:130021 )

♂ • 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

decreased skeletal muscle triglyceride level ( J:130021 )

♂ • during hyperinsulinemic-euglycemic clamps, intramuscular triglyceride levels are reduced by almost 90%

cellular

decreased adipocyte glucose uptake ( J:130021 )

♂ • insulin-stimulated glucose uptake in brown adipose tissue is reduced during hyperinsulinemic-euglycemic clamps

increased adipocyte glucose uptake ( J:130021 )

♂ • insulin-stimulated glucose uptake in white adipose tissue is increased more than 3-fold during hyperinsulinemic-euglycemic clamps

decreased muscle cell glucose uptake ( J:130021 )

♂ • 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		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:130021