Phenotypes Associated with This Genotype

Genotype
MGI:3629188

• Allelic Composition: Akt2^tm1.1Mbb/Akt2^tm1.1Mbb
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

homeostasis/metabolism

hyperglycemia ( J:71491 )

• homozygotes develop into adulthood without apparent growth defects but exhibit a mild but significant fasting hyperglycemia, which is more pronounced during fed states

increased circulating insulin level ( J:71491 )

• homozygotes develop inadequate compensatory hyperinsulinemia

impaired glucose tolerance ( J:71491 )

• in response to oral glucose load, 2-mo-old homozygotes display a mild glucose intolerance, with increased blood glucose levels at all time points measured

insulin resistance ( J:71491 )

• in response to i.p. administration of insulin, homozygotes display significantly elevated blood glucose levels relative to wild-type mice at all time points measured (at 60 min; 70.8 7.9 mg/dl vs 22.3 1.1 mg/dl, respectively)

• in euglycemic-hyperinsulinemic clamp expts, homozygotes exhibit peripheral insulin resistance along with complete failure of insulin to suppress hepatic glucose output

• however, circulating free fatty acid concentrations remain normal

muscle

decreased muscle cell glucose uptake ( J:71491 )

• insulin-stimulated hexose uptake into the glycolytic extensor digitorum longus (EDL) muscle is severely blunted in the presence of 0.33 nM insulin; however, no impairment is noted upon exposure of the mutant EDL to a higher insulin concentration (13.3 nM)

• insulin-stimulated deoxyglucose uptake into the oxidative soleus muscle is not significantly impaired at either an intermediate or maximal concentration of insulin

endocrine/exocrine glands

increased pancreatic islet number ( J:71491 )

• pancreata from 2- to 3-month-old male homozygotes respond to insulin resistance with an increase in islet mass (~4-fold) and number (~2-fold) relative to wild-type mice

adipose tissue

decreased adipocyte glucose uptake ( J:71491 )

• in euglycemic-hyperinsulinemic clamp studies, insulin-stimulated hexose uptake is mildly impaired in mutant adipocytes

cellular

decreased adipocyte glucose uptake ( J:71491 )

• in euglycemic-hyperinsulinemic clamp studies, insulin-stimulated hexose uptake is mildly impaired in mutant adipocytes

decreased muscle cell glucose uptake ( J:71491 )

• insulin-stimulated hexose uptake into the glycolytic extensor digitorum longus (EDL) muscle is severely blunted in the presence of 0.33 nM insulin; however, no impairment is noted upon exposure of the mutant EDL to a higher insulin concentration (13.3 nM)

• insulin-stimulated deoxyglucose uptake into the oxidative soleus muscle is not significantly impaired at either an intermediate or maximal concentration of insulin

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:71491