Beta cells synthesize and store insulin which is released as requirement arises. I am interested to examine the insulin synthesizing capacity of beta cells so essentially this will involve depletion of all existing insulin store and examining insulin production in response to suitable stimuli in a time dependent manner. Any suggestions, reference, ideas are welcome.
Dear Ajit Vikram,
I will try to answer your question based on the fact that the group I work with has been working with insulin for a while.
The approach they follow is called mathematical biology or dry biology if your prefer, therefore, the answer is somehow biased.
"Beta cells synthesize and store insulin which is released as requirement arises", okay, in general it comes from glucose direct and indirect stimuli, insulin starts to be produced even before the glucose achieve the bloodstream.
When you say "I am interested to examine the insulin synthesizing", I suppose you are talking about mathematical models, if so, I can given you two references:
P. Palumbo, S. Ditlevsen, A. Bertuzzi, A. De Gaetano, Mathematical modeling of the glucose–insulin system: A review, Mathematical Biosciences 244 (2013) 69–81. [citado 2015 Apr. 22]. Disponível em: http://www.sciencedirect.com/science/article/pii/S0025556413001302.
James Keener James Sneyd. Mathematical Physiology. Spring. 2009.
Andrea De Gaetano, Claudio Gaz, Pasquale Palumbo, Simona Panunzi.
A Unifying Organ Model of Pancreatic Insulin
Secretion. PlusOne.
All these references, you will find mathematical models for that.
See that according to the best of my knowledge, insulin-beta-cells modeling is an ongoing research, new works are published from time to time. Thus, you may reach points that have not been addressed in the literature; maybe even finding a starting point for a serious research, culminating in a nice paper. Of course it takes time and hard work.
"this will involve depletion of all existing insulin store and examining insulin production in response to suitable stimuli in a time dependent manner." I believe you are talking about diabetes, one of the causes is that the pancreas is "attacked" by antibodies, the beta cells are destroy and the person will need exogenous insulin for their whole life, see just for curiosity
https://www.youtube.com/watch?v=fRX6Tv9EYH8
If I happen to have more details, I will come back to you.
Do not hesitate to add your comments.
All the best,
Jorge Pires,
Is there a specific reason you need to determine the absolute insulin synthetic capacity of beta cells - or in other words, what is it that are hoping accomplish?
Under normal versus challenging circumstances, normal beta cells are capable of synthesizing insulin in quantities that differ quite significantly.
As you must already know, if you attempt to deplete insulin by physiological means - sustained exposure to severe hyperglycemia - normal response of beta cells, will include increased transcription (~4 fold increase in mRNA) and translation of insulin mRNA. When that does not seem enough, beta cells will go through hypertrophy and hyperplasia as a normal compensatory response (~3-4 fold increase in area on pancreatic sections). As you approach degranulation of secretory vesicles, some of the insulin that is secreted will be partially processed and not fully active - would you count fully processed insulin, which happens in secretory granules, in your estimated capacity?
Normally, one relies on functional challenge and estimates the capacity of endocrine pancreas to respond to the experimental challenge.
hello Ajit sir,
I don't have an exact correlation, but dithizone staining might help. It's the stain which binds to zinc in beta cells. If we can find the correlation between Zn amount and insulin synthesizing capacity, we can use that data to find the capacity of insulin synthesis.
Thanks Jorge Pires, Tausif Alam, and Heta for suggestions. These are very interesting points. I am currently going through the mathematical modeling aspect but kind of math involved in these papers are too complicated for me. I ll update you people if I get some solution to the question. Thanks once gain for the suggestions.
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