A
Andrew B. Chung, MD/PhD
Guest
kumar wrote:
> Andrew B. Chung, MD/PhD wrote:
> > kumar wrote:
> > > Andrew B. Chung, MD/PhD wrote:
> > > > kumar wrote:
> > > > > Andrew B. Chung, MD/PhD wrote:
> > > > > > kumar wrote:
> > > > > > > I have following quastions:-
> > > > > > >
> > > > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > > > on diabetic patients?
> > > > > >
> > > > > > It is not a recognized problem clinically.
> > > > >
> > > > > It looks bit odd that long acting exogenous insulin can persist for
> > > > > long but endogenous not.
> > > >
> > > > The exogenous long-acting insulin resides in a different body
> > > > compartment (subcutaneous).
> > >
> > > What will happen when long acting insulin is given intravenously?
> >
> > It becomes short acting.
> >
> Ok, but can diffused/filtered insulin in other compartments can
> polymerize and become long acting?
Exogenous "long-acting" formulations can exist in the subcutaneous
compartment in the non-physiological form.
> > > I think insulin in polymeric condition is preserved in low pH or with
> > > zinc. Higher body pH said to monomerize it. Do slow monomerization or
> > > long acting is due to lesser blood suply in subcutaneous tissues?
> >
> > There is no comparing the subcutaneous body compartment with the
> > vascular body compartment.
> >
> > > What
> > > is the normal pH of subcutaneous tissues?
> >
> > Neutral pH around 7.4
> >
> How then long acting insulin become short acting in blood but persist
> for long in subcutaneous tissues?
Because of inadequate buffering in the subcutaneous environment, the
local pH at the injection site will follow the pH of the injection
solution.
> > > > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > > > long after injecting it? Can it also remain in polymer state for
> > > > > > > prolonged time(more than as indicated)?
> > > > > >
> > > > > > The exact pharmacokinetics will vary from person to person.
> > > > >
> > > > > What causes variations in pharmacokinetics of insulin from person to
> > > > > person?
> > > >
> > > > One factor is the amount of subcutaneous body fat.
> > >
> > > How amount of subcutaneous body fat causes variations in
> > > pharmacokinetics of insulin from person to person?
> >
> > More body fat means slower release of insulin into the bloodstream.
> >
> > > Is it due to as I
> > > mentioned as above?
> >
> > No.
> >
> Then how it happens;More body fat means slower release of insulin into
> the bloodstream?
More body fat increases the distance from the injection site to the
vascular compartment.
> > > > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > > > utilized for other purposes?
> > > > > >
> > > > > > The purpose of insulin is to act on target organs as a hormone.
> > > > >
> > > > > Yes, but whether all insulin is utilized or not?
> > > >
> > > > Hormones are not substrates but rather they are signalling molecules.
> > > >
> > > How insulin can perform other actions than causes glucose into the
> > > cells without its excessive/additional presence?
> >
> > Insulin is a signalling molecule that interacts with its receptor,
> > activating it to phosphorylate other proteins at tyrosines to start a
> > cascade of post-translation modification leading to enhance glucose
> > transport into the cell.
> >
> Let us say, suppose one million molecules of insulin is reqired to
> transport 100 million molecules of glucose into the cells in a healthy
> non-diabetic person and as such all molecules of insulin and all
> molecules of glucose are metabolized.
The insulin is not metabolized in the process of interacting with its
receptors.
> What will be the appx. ratio in
> diabetic type2 with insulin resistance patient and whether all
> molecules of insulin will be metabolized in latter types?
See above.
> > > How it it diverted to
> > > perform other actions without causing hypoglycemia?
> >
> > Insulin serves to signal need for glucose uptake at target organs.
> >
> Do you want to tell that defficiency of insulin either real or due to
> its ineffectiveness avtivate body's signals to perform other actions as
> indicated in link I first provided? In other sense, insulin is not
> directly required to perform other actions as indicated in link than
> pursuing glucose entry into cells but its defficiency just trigger
> other actions. ??
It is the interaction with its receptor that brings about its effects
and this interaction is reversible because it does not lead to the
catabolism of the insulin. This interaction is concentration-dependent
defined by a binding constant.
> > > > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > > > those can be quite harmful?
> > > > > >
> > > > > > Excessive insulin can result in hypoglycemic shock.
> > > > >
> > > > > Sorry but there are many other actions of insulin.
> > > >
> > > > Only when physiological and not excessive.
> > >
> > > To perform other functions than to cause glucose into the cells, extra
> > > insulin is needed to be available.
> >
> > No.
> >
> > > How such extra insulin stop acting
> > > for its gulocose related actions and start performing other actions
> > > without causing hypoglycemia shocks?
> >
> > The effects are a function of insulin concentration and not absolute
> > number of insulin molecules.
> >
> > > > > Whether hypoglycemic
> > > > > shock is pre other actions or after all possible actions of available
> > > > > insulin?
> > > >
> > > > Excessive amounts of insulin will kill before doing anything else.
> > >
> > > Instead of this, can't it be polymerize due to its
> > > concentration(concentration is a reason for its polymerization),
> > > degrade/denature or become otherwise in-efective esp. in diabetic T2
> > > people?
> >
> > Not in the bloodstream at physiological concentrations.
> >
> > >
> > > > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > > > f insulin is not working?
> > > > > >
> > > > > > Insulin remains a functional molecule even in insulin resistant
> > > > > > diabetics.
> > > > >
> > > > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > > > without hypoglycemic shocks due to some disorder?
> > > >
> > > > If there is no hypoglycemia, the amount of insulin is not excessive.
> > >
> > > Whether normal range of insulin in blood of T2 people can be different
> > > than non-diabetic people?
> >
> > It can be somewhat more.
>
> What such more insulin can cause, how it will signal other actions?
Through its receptors which when activated phosphorylates specific
intracellular proteins involved in increasing glucose uptake and
growth.
Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:
http://tinyurl.com/cpayh
For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:
http://tinyurl.com/bgfqt
Prayerfully in Christ's love,
Andrew
http://tinyurl.com/8juld
> Andrew B. Chung, MD/PhD wrote:
> > kumar wrote:
> > > Andrew B. Chung, MD/PhD wrote:
> > > > kumar wrote:
> > > > > Andrew B. Chung, MD/PhD wrote:
> > > > > > kumar wrote:
> > > > > > > I have following quastions:-
> > > > > > >
> > > > > > > 1. Whether enogenous molecules can polymerize in dimers, tetramers,
> > > > > > > hexamers etc. alfter secretion? If yes, what can be their implications
> > > > > > > on diabetic patients?
> > > > > >
> > > > > > It is not a recognized problem clinically.
> > > > >
> > > > > It looks bit odd that long acting exogenous insulin can persist for
> > > > > long but endogenous not.
> > > >
> > > > The exogenous long-acting insulin resides in a different body
> > > > compartment (subcutaneous).
> > >
> > > What will happen when long acting insulin is given intravenously?
> >
> > It becomes short acting.
> >
> Ok, but can diffused/filtered insulin in other compartments can
> polymerize and become long acting?
Exogenous "long-acting" formulations can exist in the subcutaneous
compartment in the non-physiological form.
> > > I think insulin in polymeric condition is preserved in low pH or with
> > > zinc. Higher body pH said to monomerize it. Do slow monomerization or
> > > long acting is due to lesser blood suply in subcutaneous tissues?
> >
> > There is no comparing the subcutaneous body compartment with the
> > vascular body compartment.
> >
> > > What
> > > is the normal pH of subcutaneous tissues?
> >
> > Neutral pH around 7.4
> >
> How then long acting insulin become short acting in blood but persist
> for long in subcutaneous tissues?
Because of inadequate buffering in the subcutaneous environment, the
local pH at the injection site will follow the pH of the injection
solution.
> > > > > > > 2. Whether exogenous long acting insulin remain in polymer form for
> > > > > > > long after injecting it? Can it also remain in polymer state for
> > > > > > > prolonged time(more than as indicated)?
> > > > > >
> > > > > > The exact pharmacokinetics will vary from person to person.
> > > > >
> > > > > What causes variations in pharmacokinetics of insulin from person to
> > > > > person?
> > > >
> > > > One factor is the amount of subcutaneous body fat.
> > >
> > > How amount of subcutaneous body fat causes variations in
> > > pharmacokinetics of insulin from person to person?
> >
> > More body fat means slower release of insulin into the bloodstream.
> >
> > > Is it due to as I
> > > mentioned as above?
> >
> > No.
> >
> Then how it happens;More body fat means slower release of insulin into
> the bloodstream?
More body fat increases the distance from the injection site to the
vascular compartment.
> > > > > > > 3. Whether some insulin is not utilized for glucose intake by target
> > > > > > > cells due to insulin resistance or otherwise? If yes, does it wasted or
> > > > > > > utilized for other purposes?
> > > > > >
> > > > > > The purpose of insulin is to act on target organs as a hormone.
> > > > >
> > > > > Yes, but whether all insulin is utilized or not?
> > > >
> > > > Hormones are not substrates but rather they are signalling molecules.
> > > >
> > > How insulin can perform other actions than causes glucose into the
> > > cells without its excessive/additional presence?
> >
> > Insulin is a signalling molecule that interacts with its receptor,
> > activating it to phosphorylate other proteins at tyrosines to start a
> > cascade of post-translation modification leading to enhance glucose
> > transport into the cell.
> >
> Let us say, suppose one million molecules of insulin is reqired to
> transport 100 million molecules of glucose into the cells in a healthy
> non-diabetic person and as such all molecules of insulin and all
> molecules of glucose are metabolized.
The insulin is not metabolized in the process of interacting with its
receptors.
> What will be the appx. ratio in
> diabetic type2 with insulin resistance patient and whether all
> molecules of insulin will be metabolized in latter types?
See above.
> > > How it it diverted to
> > > perform other actions without causing hypoglycemia?
> >
> > Insulin serves to signal need for glucose uptake at target organs.
> >
> Do you want to tell that defficiency of insulin either real or due to
> its ineffectiveness avtivate body's signals to perform other actions as
> indicated in link I first provided? In other sense, insulin is not
> directly required to perform other actions as indicated in link than
> pursuing glucose entry into cells but its defficiency just trigger
> other actions. ??
It is the interaction with its receptor that brings about its effects
and this interaction is reversible because it does not lead to the
catabolism of the insulin. This interaction is concentration-dependent
defined by a binding constant.
> > > > > > > 4. Whether excess insulin, if present due to excess secretion or
> > > > > > > stimulated by medicines or injected, will cause above indicated actions
> > > > > > > in excess or not in insulin resistant patients? It looks if in excess
> > > > > > > those can be quite harmful?
> > > > > >
> > > > > > Excessive insulin can result in hypoglycemic shock.
> > > > >
> > > > > Sorry but there are many other actions of insulin.
> > > >
> > > > Only when physiological and not excessive.
> > >
> > > To perform other functions than to cause glucose into the cells, extra
> > > insulin is needed to be available.
> >
> > No.
> >
> > > How such extra insulin stop acting
> > > for its gulocose related actions and start performing other actions
> > > without causing hypoglycemia shocks?
> >
> > The effects are a function of insulin concentration and not absolute
> > number of insulin molecules.
> >
> > > > > Whether hypoglycemic
> > > > > shock is pre other actions or after all possible actions of available
> > > > > insulin?
> > > >
> > > > Excessive amounts of insulin will kill before doing anything else.
> > >
> > > Instead of this, can't it be polymerize due to its
> > > concentration(concentration is a reason for its polymerization),
> > > degrade/denature or become otherwise in-efective esp. in diabetic T2
> > > people?
> >
> > Not in the bloodstream at physiological concentrations.
> >
> > >
> > > > > > > 5. How a insulin resistant patient can get hypoglycemic effect--in view
> > > > > > > f insulin is not working?
> > > > > >
> > > > > > Insulin remains a functional molecule even in insulin resistant
> > > > > > diabetics.
> > > > >
> > > > > Yes but may not completely/efficiently, Can't there be excess insulin
> > > > > without hypoglycemic shocks due to some disorder?
> > > >
> > > > If there is no hypoglycemia, the amount of insulin is not excessive.
> > >
> > > Whether normal range of insulin in blood of T2 people can be different
> > > than non-diabetic people?
> >
> > It can be somewhat more.
>
> What such more insulin can cause, how it will signal other actions?
Through its receptors which when activated phosphorylates specific
intracellular proteins involved in increasing glucose uptake and
growth.
Will be available to "glow" and chat about this and other things like
cardiology, diabetes, cooking and nutrition that interest those
following this thread here during the next on-line chat (02/02/06) from
6 to 7 pm EST:
http://tinyurl.com/cpayh
For those who are put off by the signature, my advance apologies for
how the LORD has reshaped me:
http://tinyurl.com/bgfqt
Prayerfully in Christ's love,
Andrew
http://tinyurl.com/8juld