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 An Efficient Reprogramming Method for Human Induced Pluripotent Stem Cells (hiPSCs) Generation

 

  • Principal Investigator
    • Chul-Ho Lee, Laboratory Animal Resource Center / September 2013

  • R&D Background 
    •  Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder with diverse pathological manifestations and is often associated with abnormal regulation of hepatic glucose production. Many nuclear receptors known to control the hepatic gluconeogenic program are potential targets for the treatment of T2DM and its complications. Nevertheless, the therapeutic potential of the estrogen-related receptor γ (ERRγ) in T2DM remains unknown. In this study, we show that the nuclear receptor ERRγ is a major contributor to hyperglycemia under diabetic conditions by controlling hepatic glucose production.

  • Research Summary 
    • We have checked hepatic ERRγ expression induced by fasting and diabetic conditions resulted in elevated levels of gluconeogenic gene expression and blood glucose in wild-type mice. Also, we were able to recognize that the ablation of hepatic ERRγ gene expression reduced the expression of gluconeogenic genes and normalized blood glucose levels in mouse models of T2DM: db/db and diet-induced obesity (DIO) mice. In addition, a hyperinsulinemic-euglycemic clamp study and long-term studies of the antidiabetic effects of ERRγ-specific inverse agonist, in db/db and DIO mice demonstrated that the ERRγ-specific inverse agonist normalizes hyperglycemia mainly through inhibition of hepatic glucose production.  

  • Applied Cases and Effects
    •  Our findings suggest that the ability of inverse agonist of ERRγ to control hepatic glucose production can be used as a novel therapeutic approach for the treatment of T2DM.



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