PhD student, glucose transport and protein trafficking unit
Molecular mechiasms influencing insulin action and glucose transport in the expanding adipocyte.
To accommodates surplus energy, the subcutaneous adipose tissue rapdily expands by increasing both the adipose cell size (hypertrophy) and cell number (hyperplasia). The presence of enlarged, hypertrophic adipocytes is a key characteristic of impaired adipose tissue function, and large adipocytes are known to have reduced insulin response and impaired capacity to store additional fal. Instead, excess energy accumulates in other organs (liver, uscle and visceral adipose tissue) as ectopic fat, where it contributes to peripheral insulin resistance. Maintained adipocyte function is essential for whole body energy- and glucose homeostasis, and obesity is one of the main risk factors driving insulin resistance and type 2 diabetes. Still, the molecular mechanisms causing adipocyte dysfunction and insulin resistance remain unknown.
- Insulin secretion and glucose clearance will be monitored in vivo following i.p. glucose tolerance test.
- Protein expression and degree of phosphorylation of specific target in tissues (mainly adipose tissue, liver and muscle) and isolated cells will be analyzed by western blot.
- Establish and characterize an animal model for in vivo transduction for adenoviral-induced expression.
- Insulin response will be verified by glucose uptaketracer assays.
- Employ a variety of light microscopy analyses to examine cellulair phenotype.
- sIRNA-mediate gene silencing and adenoviral-generated overexpression of target proteins.
- Optimize culture and differentiation of human adipocyte stem cells into mature adipocytes.
- Cell size distribution analysis will be conducted using a coulter counter system.
- Interconnect experimentally collected data by mathematical modelling using ordinary differential equations.