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Post by sayhey24 on Sept 11, 2017 20:17:10 GMT -5
I don't know about the zinc but whats more concerning to me are long term effects of the analogs. No one is really sure about long term effects. BP seems to be suppressing most studies. We know what happened with the AspB10. Given the choice between the human molecule and a GMO analog, I think most people would take the human if it worked as good. In afrezza's case better.
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Post by agedhippie on Sept 11, 2017 20:54:26 GMT -5
The fastest RAA is Apidra. It becomes a monomeric in around 15 to 20 seconds once it hits the blood stream. Novolog and Humalog are slower, around 5 to 6 minutes. Mostly the whole monomer thing is irrelevant because RAA is engineered to remain largely monomeric so there is quite enough monomeric insulin to serve while the rest is converted over the next 5 minutes or so.
Apidra is the poster child for why delivery matters more than insulin form. Here you have an insulin which converts so fast it may as well be thought of as monomeric and yet it has only marginally better performance than other RAA. This is because it has to be leached out of the injection site into the blood stream - that is where RAA's slow characteristics comes from. Afrezza does not have that handicap, it passes almost immediately into the blood stream and so it behave more like IV insulin than injected insulin. There is nothing magic in the insulin.
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Post by itellthefuture777 on Sept 11, 2017 21:16:46 GMT -5
Ok..so We are not solving anything..zinc is needed in the body...the main point I think is the monomer is the most active of the insulin molecules at the end of the day...everything else..slower..
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Post by itellthefuture777 on Sept 11, 2017 21:20:36 GMT -5
The monomer is the ..most active human insulin..unbonded..
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Post by itellthefuture777 on Sept 11, 2017 21:31:14 GMT -5
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Post by itellthefuture777 on Sept 11, 2017 21:31:59 GMT -5
Significantly, when the Technosphere particles dissociate, we believe that the insulin that is released is in a form that can be more readily used by the body. In most pharmaceutical dosage forms, regular human insulin exists as a hexamer, a complex of six associated insulin molecules. In order to exert a pharmacological effect, the hexamer must first dissociate into three dimers — complexes of two insulin molecules — which then further dissociate into individual insulin molecules, or monomers. Only insulin monomers can attach to the insulin receptor and exert a physiological effect. Rapid-acting insulin analogs are designed to be fragile hexamers that dissociate more quickly, thereby reducing the time required to achieve an effect, but this is still far slower than insulin that is released from a healthy pancreas. However, the insulin released from Technosphere particles is already largely in monomeric form. During the manufacture of Technosphere Insulin, we cause hexameric insulin to dissociate into monomeric insulin before being loaded onto Technosphere particles. When Technosphere Insulin particles dissolve in the deep lung, the insulin that is released diffuses across a thin layer of cells to reach the bloodstream. Little change is required before the insulin can rapidly exert its glucose-lowering effect in the body.
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Post by mango on Sept 11, 2017 21:48:08 GMT -5
Zinc stabilizes the insulin hexamer. Located in the center of the insulin hexamer is Glutamate 13 in the B-chain joining the charge repulsion, 3 negative charges. In the blood capillaries there is Glutamate. Glutamate activates the dissociation of the insulin hexamer that was once stabilized by zinc.
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Post by sayhey24 on Sept 12, 2017 5:31:58 GMT -5
The fastest RAA is Apidra. It becomes a monomeric in around 15 to 20 seconds once it hits the blood stream. Novolog and Humalog are slower, around 5 to 6 minutes. Mostly the whole monomer thing is irrelevant because RAA is engineered to remain largely monomeric so there is quite enough monomeric insulin to serve while the rest is converted over the next 5 minutes or so. Apidra is the poster child for why delivery matters more than insulin form. Here you have an insulin which converts so fast it may as well be thought of as monomeric and yet it has only marginally better performance than other RAA. This is because it has to be leached out of the injection site into the blood stream - that is where RAA's slow characteristics comes from. Afrezza does not have that handicap, it passes almost immediately into the blood stream and so it behave more like IV insulin than injected insulin. There is nothing magic in the insulin. Agreed, its all about the speed of absorption so it gets in the blood. You say RAA is engineered to remain largely monomeric. My understanding is a small amount maybe 5-10% is a monomer. Do you have info per RAA/dimer/monomer % hexamer, ? I have never seen a comparison chart. Its also about the repeat-ability of absorption for all the math models these Tech companies like Ondou are developing. With afrezza its generally always the same. With the others there are other factors like injection site and hydration. Bottom line is nothing is as fast in and out as afrezza and as predictable. Also for me, I would also rather have the human insulin rather than a GMO.
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Post by dreamboatcruise on Sept 12, 2017 10:03:32 GMT -5
The fastest RAA is Apidra. It becomes a monomeric in around 15 to 20 seconds once it hits the blood stream. Novolog and Humalog are slower, around 5 to 6 minutes. Mostly the whole monomer thing is irrelevant because RAA is engineered to remain largely monomeric so there is quite enough monomeric insulin to serve while the rest is converted over the next 5 minutes or so. Apidra is the poster child for why delivery matters more than insulin form. Here you have an insulin which converts so fast it may as well be thought of as monomeric and yet it has only marginally better performance than other RAA. This is because it has to be leached out of the injection site into the blood stream - that is where RAA's slow characteristics comes from. Afrezza does not have that handicap, it passes almost immediately into the blood stream and so it behave more like IV insulin than injected insulin. There is nothing magic in the insulin. Agreed, its all about the speed of absorption so it gets in the blood. You say RAA is engineered to remain largely monomeric. My understanding is a small amount maybe 5-10% is a monomer. Do you have info per RAA/dimer/monomer % hexamer, ? I have never seen a comparison chart. Its also about the repeat-ability of absorption for all the math models these Tech companies like Ondou are developing. With afrezza its generally always the same. With the others there are other factors like injection site and hydration. Bottom line is nothing is as fast in and out as afrezza and as predictable. Also for me, I would also rather have the human insulin rather than a GMO. It does appear that it isn't as simple as they first portrayed with RAA's... i.e. if you read wiki page it makes it sound like RAA's do consist mainly of monomer. Apparently it is considerably more complicated. There are different forms of hexamers, and RAA's do form a fair amount (apparently, from some sampling of papers I've run across), but they are less stable versions of hexamers. There is a notation for the different versions... something like R6 vs T3R3 or some such. All of the differences in speed, however, only relate to the time it takes to migrate through fat tissue, get to a capillary and pass through the capillary wall into blood. After it hits bloodstream all insulin rapidly converts to monomers (other than basals, which may or may not, based on what I know since I've done next to no reading on them). Though bottom line... without adding additional context of delivery route it isn't true to say monomers are faster in any relevant way vs hexamers since endogenous insulin (released as hexamers) is as fast as monomeric Afrezza.
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Post by mango on Sept 12, 2017 12:58:49 GMT -5
Agreed, its all about the speed of absorption so it gets in the blood. You say RAA is engineered to remain largely monomeric. My understanding is a small amount maybe 5-10% is a monomer. Do you have info per RAA/dimer/monomer % hexamer, ? I have never seen a comparison chart. Its also about the repeat-ability of absorption for all the math models these Tech companies like Ondou are developing. With afrezza its generally always the same. With the others there are other factors like injection site and hydration. Bottom line is nothing is as fast in and out as afrezza and as predictable. Also for me, I would also rather have the human insulin rather than a GMO. It does appear that it isn't as simple as they first portrayed with RAA's... i.e. if you read wiki page it makes it sound like RAA's do consist mainly of monomer. Apparently it is considerably more complicated. There are different forms of hexamers, and RAA's do form a fair amount (apparently, from some sampling of papers I've run across), but they are less stable versions of hexamers. There is a notation for the different versions... something like R6 vs T3R3 or some such. All of the differences in speed, however, only relate to the time it takes to migrate through fat tissue, get to a capillary and pass through the capillary wall into blood. After it hits bloodstream all insulin rapidly converts to monomers (other than basals, which may or may not, based on what I know since I've done next to no reading on them). Though bottom line... without adding additional context of delivery route it isn't true to say monomers are faster in any relevant way vs hexamers since endogenous insulin (released as hexamers) is as fast as monomeric Afrezza.
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Post by dreamboatcruise on Sept 12, 2017 13:04:54 GMT -5
mango... one has to consider pancreas is creating squirts of insulin every five minutes or so, so unlike Afrezza it isn't a one shot deal when you eat.
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Post by agedhippie on Sept 12, 2017 13:09:57 GMT -5
mango ... one has to consider pancreas is creating squirts of insulin every five minutes or so, so unlike Afrezza it isn't a one shot deal when you eat. Insulin pumps also do pulsed releases to mimic the pancreas
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Post by mango on Sept 12, 2017 13:18:04 GMT -5
mango ... one has to consider pancreas is creating squirts of insulin every five minutes or so, so unlike Afrezza it isn't a one shot deal when you eat. Endogenous insulin released in hexamer form is not as fast as inhaling Afrezza in monomer form. Afrezza initiates the first phase insulin response so dang fast it acts as an exogenous regulator of glucose homeostasis—the tight regulation of blood sugar. Perhaps the most meaningful and useful invention humankind has seen in a long while.
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Post by itellthefuture777 on Sept 12, 2017 15:28:53 GMT -5
mango ... one has to consider pancreas is creating squirts of insulin every five minutes or so, so unlike Afrezza it isn't a one shot deal when you eat. Endogenous insulin released in hexamer form is not as fast as inhaling Afrezza in monomer form. Afrezza initiates the first phase insulin response so dang fast it acts as an exogenous regulator of glucose homeostasis—the tight regulation of blood sugar. Perhaps the most meaningful and useful invention humankind has seen in a long while. Exactly!
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Post by careful2invest on Sept 12, 2017 15:32:41 GMT -5
Endogenous insulin released in hexamer form is not as fast as inhaling Afrezza in monomer form. Afrezza initiates the first phase insulin response so dang fast it acts as an exogenous regulator of glucose homeostasis—the tight regulation of blood sugar. Perhaps the most meaningful and useful invention humankind has seen in a long while. Exactly! It will be great when the nations top Diabetes experts start saying this! The sky is the limit! GLTA!
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