BioSysBio:abstracts/2007/John Cumbers

Constructing an insulin sensitive cell

Authors:John Cumbers, Brown University, RI USA, 02912.
Contact:email: John underscr cumbers at brown.edu
Keywords: 'Insulin signaling' 'modeling' 'diabetes' 'cyclic' 'chaos' 'meal frequency'

Introduction

(This is just an example) Models are used to make predictions about biological systems. When making a model some simplifications must be made to make the problem tractable. A negative feedback mechanism has recently been shown to regulates insulin receptor levels and a model of the insulin-signaling pathway is presented here using differential equations. The output displays the key characteristics of this negative feedback loop under two different inputs. When fed a constant input of nutrients (a typical diet in the USA), the model mimics reduced receptor number and reduced sensitivity, which would in turn lead to higher glucose levels and over production of insulin by the pancreas (a pre-diabetic state). Pancreatic beta cell burn out is the pathology of diabetes, so then when no more insulin can be produced the patient has type II diabetes. However, when fed a cyclic input of nutrients (a more natural diet evolved from a hunter gatherer) the model exhibits normal cyclic output of insulin and no diabetes.

Results

Photo above is of insulin like peptide stained in the fruit fly brain. Our lab studies the role of insulin during old age.

A closer look of the top part of the neuron cluster shows the two halves of the brain and a central nerve, carrying insulin to the heart.

Blah Blah... How accurate is this model and are the elements presented in the equations sufficient to show insulin-like oscillations in vivo? To test if the model accurately represents the key components of the real biological system we propose a design to synthetically engineer a replica model in vivo. We propose to report the cyclic dynamics of the system with fluorescent cell surface reporters in place of insulin receptors. Future work could then investigate if an engineered metabolically robust cell can maintain homeostasis by signalling through this negative feedback loop, opening the way for synthetic interventions in the treatment of diabetes.

The table's caption

Column heading 1	Column heading 2	Column heading 3
Row heading 1	Cell 2	Cell 3
Row heading A	Cell B	Cell C

from Wikipedia

Methods

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Conclusion

Blah blah How accurate is this model and are the elements presented in the equations sufficient to show insulin-like oscillations in vivo? To test if the model accurately represents the key components of the real biological system we propose a design to synthetically engineer a replica model in vivo. We propose to report the cyclic dynamics of the system with fluorescent cell surface reporters in place of insulin receptors. Future work could then investigate if an engineered metabolically robust cell can maintain homeostasis by signalling through this negative feedback loop, opening the way for synthetic interventions in the treatment of diabetes.