Summary
This project investigates the cellular, molecular, and genetic crosstalk between differing mechanisms of insulin resistance, specifically comparing lipid-induced, androgen-induced, and diet-induced forms.
The cellular molecular regulation of differing mechanisms of insulin resistance.
US · IL
NIH
grant
closed
#nih-5R01DK126892-04
What they want
The project aims to establish that differing causes of insulin resistance display crosstalk between cellular, molecular, and genetic mechanisms. It will involve developing three mouse models of hepatic insulin resistance: high androgen (HA)-induced, high fat diet (HFD)-induced, and high fructose diet (HFrD)-induced. Using various hepatic specific knockout (KO) mice (androgen receptor (AR-KO), ketohexokinase (KHK-KO), and protein kinase C (PKC-KO)), the project will examine the intersecting pathogenic mechanisms unique to each of the three insulin resistant models.
Deliverables
- Development of three mouse models of hepatic insulin resistance (HA-induced, HFD-induced, HFrD-induced)
- Examination of intersecting pathogenic mechanisms using hepatic specific knockout mice (AR-KO, KHK-KO, PKC-KO)
- Identification of unique mechanistic aspects and crosstalk within each insulin resistance model
- Insights suggesting targeted therapeutic interventions based on insulin resistance type
Technical requirements
- Mouse models (HA-induced, HFD-induced, HFrD-induced)
- Hepatic specific knockout (KO) mice (AR-KO, KHK-KO, PKC-KO)
- Molecular and genetic analysis techniques (e.g., insulin receptor tyrosine kinase, p-AKT, glucokinase, glycogen synthase)
