Project Details
Description
It has been suggested that it may be possible to utilize the recently
developed and more readily available beta cell lines as an alternative
to islets or whole pancreas for transplantation therapy of diabetes.
We recently reported that stable transfection and overexpression of the
calcium binding protein calbindin in the rat beta cell line RIN 1046-38
results in a marked increase in insulin mRNA (greater than 20 fold for
most clones) as well as insulin content, release and transcription.
These studies provided direct evidence for a role for calbindin in beta
cell function which may have therapeutic relevance. However, RIN cells
have little or no responsiveness to glucose. For transplantation
therapy, it will be important to utilize beta cells with functions
approximating normal beta cells. Thus we propose in this exploratory
grant to further examine the role of calbindin in the beta cell using
beta-HC cells which respond to glucose and other secretagogues.
Specifically, beta-HC cells will be examined for the effect of calbindin
on basal insulin mRNA, on basal insulin content, release and
transcription, and on the response to secretagogues.
In addition we will also determine whether calbindin, which has been
reported to protect against apoptotic death of a number of different
cells, can protect against cytokine and streptozotocin (STZ) induced
destruction of rat beta cells. Possible mechanisms involved in a
protective effect of calbindin will be examined, including inhibition
of stimulation of nitric oxide production and inhibition of calpain or
interleukin 1-beta-converting enzyme protease activity. These findings
would have therapeutic implications for the prevention of beta cell
destruction which could have important application to beta cell
transplantation.
Status | Finished |
---|---|
Effective start/end date | 9/30/98 → 9/29/02 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases
ASJC
- Transplantation
- Cell Biology
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