Mouse Model for Endocrine Pancreatic Development, Insulin Secretion and Diabetes

NU 2010-071

Inventors

Joseph Bass*

Biliana Marcheva

Short Description

A mouse model based on removing the clock function within islet cells

Abstract

Northwestern researchers created a mouse model based on removing the clock function within islet cells. These mice exhibit striking defects in insulin secretion which ultimately leads to greatly accelerated early life diabetes. This model provides a direct opportunity to apply new methods to study and understand how the clock transcription network regulates aspects of endocrine pancreas function. With this understanding, it provides the opportunity to explore various means of enhancing islet function and to further develop existing or potential therapies for diabetes, such as (1) stem cell therapies for type 1 diabetes, (2) cell survival in post-transplant and/or endogenous islet function in type 1 and 2 diabetes, and (3) pharmacotherapeutic targeting for enhanced insulin secretion in type 2 diabetes. In fact, the development of clock-modulators using this platform is already underway.

Applications

• Research Tool: Animal Model
• High throughput screening for diabetes-modifying therapeutics
• Identification of methods using stem cell transplantation and cell preservation methods
• Drug Discovery for improved combination treatments with existing agents

Advantages

• Powerful tool to dissect the role of clock transcription network on endocrine pancreas function

Publications

Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH, Lopez JP, Philipson LH, Bradfield CA, Crosby SD, JeBailey L, Wang X, Takahashi JS, Bass J (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466: 627-631.