Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
We have reanalyzed the dose-response curve of that study by using WEBMAXC and have arrived at an apparent EC50 for
***TRPM4 activation of 880 nM.***
TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
TRPM4b is activated following receptor-mediated Ca2+ mobilization, representing a regulatory mechanism that controls the magnitude of Ca2+ influx by modulating the membrane potential and, with it, the driving force for Ca2+ entry through other Ca2+-permeable pathways.
PMID: 12015988
We here report that ***insulin-secreting cells*** of the rat pancreatic beta-cell line INS-1 natively ***express TRPM4 proteins*** and generate large depolarizing membrane currents in response to increased intracellular calcium.
880nM to ***activate insulin secreting cells*** ?(beta pancreatic cells) which would release insulin and lower the blood sugar.
Below...looks like IL1 B is destroying those cells.
Some viruses can trigger the same:
These studies provide biochemical evidence for a novel mechanism by which viral infection may initiate B-cell damage during the development of autoimmune diabetes.
The viral replicative intermediate dsRNA stimulates B-cell production of pro-IL-1, and following cleavage to its mature form by IFNy (that is gamma) activated ICE (IL-1B-converting enzyme) ,
***IL-1B then initiates B-cell damage*** in a nitric oxide-dependent fashion.
Type 1 diabetes is characterized by the infiltration of inflammatory cells into pancreatic islets of Langerhans, followed by the selective and progressive destruction of insulin-secreting beta cells.
Islet-infiltrating leukocytes secrete cytokines such as IL-1β and IFN-γ, which contribute to beta cell death.
In vitro evidence suggests that cytokine-induced ***activation of the transcription factor NF-κB*** is an important component of the signal triggering beta cell apoptosis (death).
Our results show in vivo that beta cell-specific activation of NF-κB is a key event in the progressive loss of beta cells in diabetes. Inhibition of this process could be a potential effective strategy for beta-cell protection.
sparkle7
Frequent Contributor (5K+ posts)
Member # 10397
posted
This is a little too technical for my brain right now... Can you translate into layman's terms?
Posts: 7772 | From Northeast, again... | Registered: Oct 2006
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