“Regrowth of beta cells with small-molecule therapy”

Type 1 Diabetes (T1D)

The Pancreas: Home of the beta cell

http://www.livescience.com/44662-pancreas.html

Beta cells sufficient

Insulin sufficient

T1D: Beta cells lost

Insulin Insufficient

The mTORC1 pathway: An important regulator of beta cell growth and division

What is it? What does it do?

mTORC1-active beta cells

Increased Cell Division

(more cells)Aylett et al. (2016) Science 321(6268):42-48

mTORC1: an enzyme complex

Increased Cell Growth(more insulin)

mTORC1

Key New Finding: Beta cells try unsuccessfully to regrow themselves before the onset of diabetes with mTORC1

But it is not enough…

Beta cells sufficient Beta cells

insufficient

Cell Growth and Division

Progression towards Diabetes

Early MidLate

mTORC1

The Goal: Regrow beta cells at a greater rate of speed with mTORC1 small molecule therapy

Efficient Beta Cell Growth and Division

small-molecule therapy

HighLow

Can we promote beta cell growth and reverse

diabetes?

Level of mTORC1 activity:

The Approach

Models:

2. T1D mice

1. Beta cells in culture

3. Human samples

1. Test known small molecules that stimulate the mTORC1 pathway

2. Screen small molecule libraries to identify new mTORC1-activating drugs

Experiments:

Intended Outcome

Beta cells sufficient

Cell Growthand Division

Progression towards Diabetes

Early MidLate

1. Prevention Reversal of diabetes

progression

2. CureRestore enough beta

cells to make sufficient insulin

mTORC1

…for taking the time to consider supporting this project and being a part of innovative early-career

T1D research!