Insulin Paradox.Has any one heard about it?

I am sure no body has heard about it. Actually it is me that is coining the word for first time.

What every body know is that in type 2 diabetes ,there is insulin resistance. So even if pancreas is working normally and there is enough insulin or may be there is hyperinsulinemia ,still insulin is not doing its work of lowering blood sugar properly. So there is hyperglycaemia .

Now, the same person who has high blood sugar level due to insulin resistance ( endogenous insulin becoming ineffective ), when given insulin from outside ( exogenous insulin ) ,responds quickly and high blood sugar level goes down. Meaning external insulin works while internal insulin is in effective. IS IT NOT A PARADOX ?

44 Replies

  • Mr Pataliputra

    I have no direct answer to your question. In a lighter vein I would ask you a counter question.

    Is it that our body is going the American way of eating fast food in a fast food joint in flat ten minutes as against French way of tediously resorting to cooking food at home from scratch and eating it for nearly two hours as lunch. Our body must be thinking why put our pancreas to work when something is readily available externally to do all the tedious work of torturous way to use it by its own effort? Or is it in any way succumbing to ADA,USDA and farma lobby's conspiracy to make money?

    Any way there appears to be an alternative to bring both BSL to its knees as well as all those lobbies without any such external or internal effort/method by just following this method.

    Thank you for inventing a third paradox.

  • Mr.Rao, let us drop "Mr.".

    Even though you have written about French dietary ritual,in a lighter vein,it has reminded me our own dietary customs. It postulates that each bite of food should be chewed 32 time before swallowing. If we could revert back to and follow that system of eating,we could perhaps surpass the French lunch duration. If that happens there will be no need for effort,internal or external,and pharma industry will go into a stage of shock.

    By the way,any thought on how to solve Insulin Paradox puzzle ?

  • Pataliputra

    I have dropped" Mr" from this blog as per your desire.

    I don't think we can avoid insulin..I myself am an insulin dependent person now for the last many years or so. I have not been able to tolerate oral diabetic medicines although I tried them in between. I was declared diabetic at age of 35 almost 47 years back .First 10 years went by only on diet. Next 25 years on short acting insulin. Under advise of doctor I tried oral drugs for 2 yers but was getting allergic sensation .I stopped these tablets and am on human mixtard30/70 which the doctor says is a good substitute for our own insulin. I eat every thing vegetarian but frugally. Once a year I get my parameters specially heart kidneys eyes etc., As per doctors all are okay. and advise me to follow the regimen .Since one year my total insulin has reduced to half. I don't know why. Is it my diet or walking habit or my body is able to manage on its own .It is a miracle. I did not have any kind of complications. May be god is favouring me .I am fairly active and mentally alert.

    I have no intention to bore youwith my personal details i thank you for taking my latest blog in the proper spirit.

  • dear rauji,

    if insulin requirement has fallen it is worth checking the kidney function

    because kidney dysfunction can prolong the half life of insulin .

    and some such thing as kidney defect

    decreasing the insulin disposal mechanism at kidney.

    thereby better insulin availability in the body.

    kindly consult some diabetologist.

    good luck

  • Rao,I am inclined to agree with Indiacratus. Falling requirement of insulin might point an accusing finger at kidney. But if your doctor says all is well, then there is no concern to worry. May I suggest a Doppler CT scan of kidney to rule out any initial renal damage . Well you are the best person to judge.

  • yes. this was done only a month is per the report.

  • Good for you,nothing to worry as far as kidney is concerned.

  • the reduction in insulin was as per advise of diabetologist who is consulted by me regularly.I do not do on my own. Further the kft test sonography etc., including urine flow etc., was done as precaution .It does not show anything. One more thing the doctor also checked for bl pressure.It is normal.I understand blood pressure increases if kidneys are sluggish.Any way I wish to know more

  • Btw, can you you quote your blood sugar levels fasting and pp and also HbA1C.your BP .sorry, if it encroaches upon your are at Liberty not to make your medical reports public.

  • fastinf bsl ossilates between 85 to 95.

    ppbsl 125/ also fluctuates.

    random after walk 10/120

    bp fluctuates 120/80 to 130 95 depending on the time at which it is taken

    HBA1c was 6.7 before one yearnow it is 6.1 about 3 months back prompting reduction in insulin intake.

    The doctor told me looking to my age slight higher bl sugar is advisable.strict control I not advised by him.

  • Your reports are wonderfully good.please continue what you are following . If you have any thing specific in mind please come out with it.Will try to clear any doubts with our limited knowledge.

    Thank you for sharing your reports.

  • thanks.for your reply.since I am on the wrong side of 80 I am very cautious.even then something can happen.It isultimately god's will that prevails.

    by the by you are from which part of india.?no need to reveal if you do not wish to

  • I come from North India. No secrets.

  • I must compliment you on your fine health. Even at the the age of about 82 yrs ,you are physically and mentally very active. I have also seen a few diabetics,on oral hypoglycemics,eating every thing including a lot of sweets,I repeat a lot of sweets,still hale and hearty and without any complications. They all are 80+ age group. I have not tried to look for the reason behind that. There must be some thing more than the diet and walking. I have also known diabetics who despite proper diet and excercise and medication including insulin, have failed to control their blood sugar.

    That is why I want to understand the phenomenon of insulin paradox as clearly as possible.

    Thanks for sharing your diabetic history.

  • It may be due to tension free life & happiness

  • dear patliputra,

    the general explanation given for hyperinsulin in blood and unable to clear the glucose is thus:

    1] insulin is received by a mechanism on the cell surface called INSULIN RECEPTOR.

    if the expression of these receptors are less in a person,

    the total 'insulin triggered activity'

    also will be less.

    but if the insulin in blood is more,

    the receptors are more likely to capture an insulin molecule.

    an analogy can clear this.

    if a fisher man casts a net into the water,

    few fish will be caught in the net

    if the water contains less fish.

    increase the number of fish in water [injecting insulin] he gets a better chance.

    2] there is another thing called insulin signalling which is not relevant in this particular case.[though a defect in this signalling beyond reception

    can cause t2dm..many scientists agree to this, but may not be relevant in hyperinsulinemia.

    in other words both endogenous and exogenous insulins work but more quantity is required in some people.which we provide by injection.

    another thing that can be considered is

    insulin somehow is altered once it enters blood from pancreas.

    but this will be same fate for external insulin and as such becomes not a significant reasoning.

    good luck

  • Indiacratus,something new for me,insulin is altered when it enters into blood from pancreas?

    The said explanation for insulin paradox never satisfies me . It is too simple . It's just like putting a crowed at a barrier, hoping some might sneak in ! It fails to explain many things. A more detail understanding of the whole subject is required.

  • dear patliputra,

    " that , insulin is altered when it enters into blood from pancreas? "

    this thing i read long ago as a possible hypothesis in an article in readers digest--

    what significance level it has is beyond the our scope.

    but there are things like anti insulin antibodies ,gad65 etc

    gad65 antibodies are often measured in t1dm beginning.

    i am not well versed in it.

    whether true or not

    our discussion is not about it because as you pointed out ,exogenous versus .....

    about the

    insulin receptor and the frequency of its appearance on the cell surface is a well known explanation.

    but i think the biochemists are nowadays more inclined to explain on the basis of post receptor signalling.

    these things are just opinions and may not be conclusively accepted by all.

    but the mechanism of insulin receptor and post receptor signalling is universally available;e in all texts and websites,.

    the fish and net analogy is my own and is in consistence with the concept of 'insulin receptor density.'

    these things are probably beyond the scope of a discussion by non professionals like us.

    good luck.

  • Indiacratus, to get to the bottom of things is my habit since younger age. There fore I have developed expertise to understand complicated things in many discipline . Once upon a time puzzle solving was my past time.

    So the crux of the matter is to understand insulin resistance . And I am not going into those details here.

  • i know you want to get to the bottom of things, explanations.

    here is an exerpt from the joslin.

    Scientists don't know exactly what causes this insulin resistance, and many expect that there are several different defects in the process of unlocking cells that cause insulin resistance. --------------------------------------------------------. Physical activity also seems to improve the body's ability to use insulin by decreasing insulin resistance, which is why activity is so important in diabetes management.

    good luck

  • insulin paradox.

    dear patliputra,

    i dont think there is any paradox.

    we do not know

    what causes insulin resistance.

    but this cannot be called a paradox.

    it is a paradox.the way you put it, if endogenous insulin does not work.

    but it does not happen like that.

    what happens is this.

    to give an example.

    suppose a normal person requires 40 units of insulin.

    his pancreas can produce a maximum of 50 units. he is now with out problems .

    when there is insulin resistance.

    suppose an insulin resistant person requires 60 units of insulin.[just some more insulin]

    his pancreas can at most produce only 50 units as in the case of the normal person..

    thus he is at hyperinsulinemia [because 40 is normal insulinemia] and hyper glucose.

    the remaining 10 units are to be pumped from outside.

    these are measurable quantities.

    measurable quanties ?both endo genous insulin and blood glucose are measurable.

    and we are able to define

    insulin to carbohydrate ratio

    and the blood sugar correctin factor.

    for one unit of insulin it is 10 grams of carbs

    and for one unit of insulin for 50 mg per dl of blood sugar.

    The insulin to carbohydrate ratio represents how many grams of carbohydrate are

    disposed by 1 unit of insulin ...

    if 1 unit of insulin will drop blood sugar by 50 points (mg/dl)

    then the high blood sugar correction factor is 50.

    both the CHO ratio and the high bs correction factor vary from individual to individual.

    and also with respect to time of the day.

    that endogenous insulin does not work needs proof.i haven't herd any such thing.could you locate a source?

    good luck.

  • What is a paradox. As per dictionary meaning "a seemingly contradictory statement but found to be true." Now on the basis of this meaning, if I say insulin paradox, is it not correct ?

    Please look at from another angle, is any of the statement made is factually incorrect ? So statement seem contradictory but is based on sound logic.

    Here we are not concerned with any correction factor or questioning the efficacy of insulin. The contradiction is that in the same environment that is blood, endogenous insulin is not effective despite there being very high level of it (hyperinsulinemia ), while in the same environment external insulin is in real life practice is effective.

    So the PARADOX is that the same insulin produced internally is not doing its job,but same insulin when given from outside does its job efficiently. It needs no reminder that both insulin ( internal and external ) are structurally the same.

  • dear patliputra


    there is a misunderstanding.

    what i wanted to say was that

    they can measure the the insulin to carb ratio with endogenous insulin as well as injected insulin.

    the ratio will be same for a given individual for a given time.otherwise paradoxical.

    it is based on certain rate of flow , anyway.

    but i will talk as though they are absolute values for a moment.

    this will be clear shortly.

    suppose you give a tablet which produces 5 units of insulin inside the body to one healthy person.

    he is simultaneously given intravenous glucose drip [and glucose adjusted by tap to get constant glucose in the blood through out the experiment.]

    the tablet in liquid form can as well be given drip by drip.

    you will see the total glucose given is 50.grams.[or let us presume it is 50 in a healthy man.

    this is called a clamp test [slightly modified for this discussion.]

    now look at the results.

    we gave medicine equal to 5 units and 50 grams of glucose

    and noticed no rise in bs.

    this means

    the tablet generated insulin disposed the 50 grams of glucose.

    so we repeat the same ,in an insulin resistant diabetic ,.

    we will get less glucose given for that amount of medicine ,that is less than the 50 grams,.

    say only 40 grams glucose was necessary to cover the insulin and glucose disposal effect.[for constant glucose in blood]

    we can repeat the the same with

    intravenous feed of insulin and glucose mixed together in a bottle into which ,the the rate of glucose can be adjusted by tap. for those persons.


    the results will be 50 and 40 respectively.

    for example

    a result of 50 for the healthy man and 45 for the resistant in the second set of experiment

    we can say external insulin was more effective.

    [40 for first= -resistant]

    the above can easily be understood by a

    person who already have an understanding of the clamp test.

    you can also certainly, if you can keep the settings correctly visualized.

    now i hope , you can agree ,why i said all these quantities are 'measurable'

    .in order to be paradoxical a result of 40 and 45 should be arrived at,.

    that is external insulin is working better.

    good luck

  • I know about clamp test since long. The paradox is not about comparing the efficacy of exogenous and endogenous insulin. I am sorry to say that you are thinking is differen and in different direction.

    When you talk about French paradox,you simply say that both French and Americans are both taking high fat diet,but French are slim and have little cardiac complications,while Americans become obese and with it all related complications. So it is paradox. Same fat different result.

    In the same way ,as natural insulin is unable to cope with the rising blood sugar level (please remember insulin is available in abundance ,much, much more than what is required ) ,the artificial insulin is effective. I may point out that whatever the cause of failure of endogenous insulin to function properly,is still there when exogenous insulin is administered.

    In vitro, while functionally and structurally both types of insulin are same,there is no two opinions about that,but in vivo in diabetics reasons unknown ,results everybody know exogenous insulin does reduce blood sugar levels. That is the paradox. Same insulin different result.

  • dear patliputra,

    somehow i have failed to catch the point.

    if exogenous and endogenous insulins behave diferently it is a measurable issue=as i explained.

    but in an insulin resistant person

    if insulin is less effective and he wants more,

    there must be some reason .

    that reason is clearly that the person is different from the non resistant person in his biology.

    what difference exist in their biology we do not know yet- what is the paradox then.

    in the french case

    both these Americans and french are more or less ethnically same and similarly industrialized nations ,. then why they differ is the paradox.

    if two mono zygotic twins -one acquires diabetes and the other does not get diabetes we can call it paradoxical..[presuming both having same set of genes and people have heredity in diabetes]

    what i meant was ,

    that science has not explained a thing and that by itself

    does not qualify it to be considered a paradox.

    if i am to step out into philosophy for a moment,

    then it is a violation of what they call the principle of identity that constitutes a paradox.

    if two things are exactly identical and if they behave diferently,

    we would counter argue that the things were not identical.

    but then some philosophers would argue that one could go on telling it ad infinitum -

    so the law of identity is not has to be a belief and not a principle in science.

    any way congrats and i am proud that many of us in the forum are rational and it should be.i mean the forum.

    good luck

  • Just following what white collared scientists say in lab doesn't mean one is rational. Rational guys weight both sides of the story without bias or prejudice and more often that not that's done based on personal experience.

    Just take a look at LUPUS forum. I just follow that forum to see how decently guys and gals behave even when they go against the so called science. No one starts bashing anyone who criticizes the mainstream. Many even say that the amount of new things that they learned no doctor could ever tell. This is how FORUM should be and not what you think it should be.

    I have read about this whole insulin paradox with half side of the story

    Was insulin in blood of the subjects measured?

    What is triglycerides level?

    How bad is IR?

    What are other drugs taken? Because STATINS are known to increase insulin resistance.

  • Indiacratus, agreed in French paradox ,ethnicity is same and the reason, perhaps is the difference in the quality of fat.whatever might be the reason,which is immaterial,only both eat high fat and result is different,so it is paradox,and we all accept it.

    Now ,function of insulin,reduction of blood sugar,universal truth.

    Hyperinsulnemia precedes development of first prediabetes and then full blown diabetes, widely accepted fact.

    Endogenous insulin,for whatever reason fail to control blood sugar level, accepted fact.

    Exogenous insulin ,when administered,reduces blood sugar,irrespective of level of insulin in blood or lipid profile data ,irrespective of ethnicity ,race or genetic profile. Accepted universally.

    So ,both endogenous and exogenous nsulin is behaving differently,in exactly in the same condition,and that also without exception. An undisputed fact.

    Is it not a PARADOX ?? It has much stronger case as it is a global phenomenon and not limited to a small group as in French paradox.

  • dear patliputra,

    "Hyperinsulnemia precedes development of first prediabetes and then full blown diabetes, widely accepted fact."


    no.this happens in few people only

    because they define diabetes as either


    zero insulin


    insufficient insulin


    insulin not working properly.

    [and 2c which is a person with both 2a and 2b--rare?]

    2]b) happens only in some people, and is called insulin resistant--

    2a and 2b together constituting t2dm.

    they are two subgroups in t2dm.


    "Exogenous insulin ,when administered,reduces blood sugar,irrespective of level of insulin in blood or lipid profile data ,irrespective of ethnicity ,race or genetic profile. Accepted universally."


    no."irrespective of level of insulin"is not precise.

    it is the sum of the two ie, the quantity of endogenous and exogenous insulins together

    reach the level required by the insulin resistant diabetic.

    that is why i said these factors are measurable quantities.


    "So ,both endogenous and exogenous nsulin is behaving differently--"



    they dont behave differently .only the quantities are diferent.

    kindly refer to my previous response where i mention 60,50,40 etc.

    suppose a insulin resistant person requires 60 units and his body produces 50 and we give 10 from outside.

    both the 10 and 50 work similarly.

    in other words if an insulin resistant person in old age produces no insulin at all

    then he will require the 60 units pumped in from outside and not the old 50.

    it has now become paradoxical that i am unable to present my case successfully.

    in general in the past,

    people considered me a person , able to present a case in simple language and few equations.

    whether i was right or wrong was beside the point.

    good luck

  • Dear Indiacratus , here we are talking about insulin and NOT diabetes. Secondly ,when I say irrespective of insulin level in blood,it is quite correct ,whether there is high level or low level external insulin is effective,so no need to measure insulin. We are not talking about even insulin resistance. You may be right when experimenting in normal subjects,but not in a diabetic,who require external insulin.

    Physiolathogenesis of insulin secretion and. It's role in glucose homeostasis in normal condition and in diabetic condition is very complicated and will need lot of time and energy to understand.

  • Sigh, the reason the American diet is bad is because it contains man-made fats, harmful carbohydrates and additives.

    Too much insulin is worse for health than hyperglycaemia; see the ACCORD study. Don't eat more carbohydrate than you use.

  • "Don't eat more carbohydrate than you use."

    Scientists say eat 60% CARBS and only 7% saturated fat and then walk 5 miles. Ridiculous.

    Everything is on the up (diabetes, obesity, cancer, cvd, chd, autism, ibs, etc after this recommendation :( :(

  • One has to understandthe inter-relation of glucose as it is insulin secretogogue. on arrival of glucose insulin released. Its action is on insulin receptor for uptake of glucose intotargeted tissue. If understands this interaction ,then one can appreciate of the pardox posed.

    Let me clarify the dynamism invovled because I worked on this extreemly useful concept.on digestion of polysaccarides at the gut enzymes, glucose is liberated ,which is absorbed by the blood, remember that they are spefic transporters,there is increase in the glucose which signals beta-ilet cells to secrete insulin.This secretion is intune with glucose concentration as the glucose levels go up insulin increases but as glucose tapper the insulin levels do.After about two hours the blood glucose levels reach around120-140mg/ also insulin levels reaching to minimum but, secretion continues at lower level.After 4-5 hours of carbohydrate ingestion glucose levels reach much lower causing hunger and one take food.

    Maintance of glucose is very important since brain depends on glucose as source of energy, otherwise it leads to fatality.

    It is OK in day time, one feels hungry and takes carbohydrate food. As again this in night this is different. Liver gluconeogenisis takes place to maintain blood glucose levels to feed the brain.

    In type 2 diabeties gluconeogenisis is thrice higher, thus leading to higher glucose out put causing higher insulin secretion.

    This is particularly observed in fasting glucose and fasting insulin levels. This is used as marker of on set of type2 diabeties. This is calculated as HOMA values.

    So there is higher insulin but not acting, this is the pardox.

    For better understanding of this one must know the basic interlation of insulin&insulin receptors.

    For pushing glucose into target tissue, insulin acts on specific protein on cell membrane called insulin receptor.More details are not given except the fact that reaction is though one to one, the interaction is not linear to insulin concentration in blood. What this means higher the insulin ,the availability of insulin receptors on cell membranes ćome down because of internalization of insulin&insulin receptors, thus accumating more insulin in blood.This is known ad inverse relation of ligand and receptor in molecular endocrinology. It applies generally as ligand receptors complex. The net result is higher insulin less glucose is pushed. For better clearance if insulin is less then better is exposure of insulin receptors. This is insulin sensitization so many antidiabetic drugs are based on metformin like drugs which causes increased number of înśulin recptors without altering insulin essentially means the number of insulin receptos are more per molecule of insulin.

    Contratry to this in sulin resistance the number of insulin receptors levels are far less.Thus this leads less insulin receptors due to internalization thus leaving more insulin in blood, but due to shear mass action it tries to act and push glucose.

    Finally,take home point is that relation between insulin and insulin receptor is like yin-yang . Hence this distinction"


    Dr. m.K.Janardanasarma. Ph.D(IISc)

    Molecular endocrinologist.

    Deputy Director(Retd)

    National Institute of Nutrtion,p

    Indian Council of Medical Research,


    Contact number 09866822770

  • "So there is higher insulin,but nor working." That is the paradox. You clearly got to the crux of the matter. Let me explain, in diabetics, higher levels of endogenous insulin in blood is unable to act on or act insuffiently on circulating glucose,while exogenous insulin is effective . That is the paradox.

  • Actualy in type 2 diabeties, there is higher insulin in fasting state not on response to glucose load.please check what is called area under the curve of insulin rełeased called AUC for that period of time of glucose absorption from villai of intestine. Repeated ingestion of high carbohydrates results high demand on insulin secretion repeated. This causes exhustion of insulin,since the synthesed insulin is stored granules. On emptying these granules new insulin has to synthesised which takes time. Thus there is lag period. This lag period if it becomes too short if beat the beta ilets cells repeatedly with high food in take, thus resulting type 2 diabeties. This is always"less. We have repeated this in laboratory on human diabetic voluteers compared to normals.AUC of insulin falls shorter over period of time. So one is put on insulin secrtoguge to increase levels as treatment regime.

    The important point is the number of insulin receptors molecules avaible per molecule of insulin.This is crucial as pointed out,higher is the number of insulin receptors available per molecule better is glucose clerance. On the contratary as in type -2 diabeties since gluconegenis is three times higher, this leads to more fasting insulin secretion, which leads to down regulation of insulin recptors. We have actually quantifed the number of insulin receptors per molecule of insulin. In cases number of insulin receptors permolecule is so low that it corresponds to high level of glucose in plasma.

    Again inverse relation between insulin and insulin receptors is crux of pardox.

    By feeding high fiber we are able to reduce AUC of insulin,but the number of insulin recptors jumped ten to fifteen times and glucose is cleared .This is basis of using highfiber diet or lowglycemic index diet.

    All these finding editorial comments are published by in Journal of Diabeties and Metabolism 2011Sep, under title "insulin sensitization and insulin resistance quantative moleculár model in prediabetic mouse model


  • ""So there is higher insulin,but nor working." That is the paradox"

    Definitely not. The higher insulin is insufficient due to Insulin resistance.

    If IR increases even external insulin dose needs to be increased.

    So no paradox anywhere.

    Get TG/HDL close to 1 and same insulin will have far better sensitivity.

  • I am sorry to say that every one is missing the point. It is not about insulin resistance. Resistance is a common factor for both internal and external insulin. Paradox is while endogenous is ineffective or only partially effective, insulin when given from outside it works.

    If cause is set as parameter then there is no French or obesity paradoxes.

  • The quantity injected/needed is also dependent on IR. With reduced IR even endogenous insulin works better thus needing less and less of exogenous shots. Exogenous works as it makes up for the shortfall. Even exogenous shots keep increasing. Why? It's all about TG/HDL ratio and insulin deficiency. No paradox here.

    In addition, even STATIN drugs add to the woes, as it forces IR.

    French or obesity paradoxes are there because of failure to recognize the cause -- Higher INSULIN in blood -- because High Carb diet has to be pushed as healthiest diet under the sun. People don't see the main reason and talk about sedentary lifestyle ie blame the patient and not the system.

  • that may be true.

    these paradoxes were paradoxes long ago when they were described so,.

    now we are nearer to an explanation.

  • dear sarmaji,

    "In type 2 diabeties gluconeogenisis is thrice higher,---"

    this needs clarification.

    as i understood

    gluconeogenesis is the synthesis of glucose from non-carbohydrate sources, such as amino acids and

    glycogen to glucose conversion is not to be considered as ---gluconeogenesis.

    in t2dm

    in the liver ,

    it is glycogen converted glucose that reappears in the blood in the night or in general fasting inpairment of this is handled by metformin.something like closing a to -more glucose into blood.

    for otherwise :

    the glucose converted through gluconeogenesis, from protein does not appear instantly in is a long time consuming and does not raise the bs is the standard opinion .

    your description of internalisation of the recptor is not clear enough..kindly write in a simpler sequence.

    internalization of the receptor bridge and insulin together is by necessity ,

    otherwise how to degrade insulin?.

    if insulin is returned to blood it will accumulate and the purpose of stabilization will be undermined.

    the yin yang comparison is probably inappropriate ---

    what happens is ,

    what may be called a negative feedback which stabilises in a healthy man .

    i mean ,

    more insulin leading to the disappearance of both insulin and the already expressed receptors through internalisation..

    and in a diabetic improper stabilization

    as the receptor numbers are smaller as you pointed feedback,

    a system can be stabilized at any point.depending on the misbehavior of a component .

    in this forum most of us are people from other professions and are people who acquired cut piece information from net articles.

    as such you may have to right in a much more simpler style.otherwise our efforts go waste.

    thanks for response .

    come often.

    good luck.

  • Gluconegenisis is higher in type -2 it from stored glycogen or from aminoacids. Kindly refer to all articles on mechanism of action of metformin.

    Returing to the question of insulin and insulin receptors, the interaction of insulin on it receptors causeses cascade of reaction first being of autophorphorylation of tyrosine residues, then othere cell proteins called IRS-1,IRS-2 which again leads to translocation of glucose transporters from cytosol to cell surface membrane, this glucose transporter translocates glucose from blood to cytosol, eventuallt the complex of insulin and insulin receptors are englued into cytosol forming what is called clatharin pits, thus there is deprivation of insulin receptors at cell surface. The entire process is called down regulation of insulin receptors. For fresh receptors to appear on cell surface it takes lag time. Hence appearnce of new receptors would dispose fresh insulin to act upon.

    The ying-yang theory is well established in endocrinology system. For better understand let me ilustrate smelling where the odour on intital contact to nose smells, but on constant exposure smelling come down. So do nuerotransmitters, drugs used in the nervous syt.

    Kindly refer to the my article referred in the previous reply. Where there quatification of Insulin receptor per molecule of insulin,which clearly shows that number of molecules of insulin receptors per molecule is far higher compared insulin resistances where the Insulin recptors are far less per molecule of insulin.this elebborated well editors of journal.

  • "Maintance of glucose is very important since brain depends on glucose as source of energy, otherwise it leads to fatality."

    Brain can run on ketones equally well.

    Certain drug resistant epilepsy is treated with ketogenic diet where carbs are 10% or less.

  • Yes gluconegenis is three times higher in type-2 diabeties. It is synthesis of glucose from other sources. The entire story of type-2 diabeties starts from this phenonemena.Hence the first line of treatment type 2 diabeties supression of gluconeogenisis by drugs like metformin sothat there is normalization of fasting glucose. Refer to mechanism of action of metformin in good scientific journals or wikipedia.


  • dear sarmaji

    How Metformin Works?

    "Metformin helps the body to control blood sugar in several ways.

    "The drug helps type 2 diabetics respond better to their own insulin, lower the amount of sugar created by the liver, and decreasing the amount of sugar absorbed by the intestines."

    let me interpret the three points given above.

    1]"respond better to their own insulin"


    this is what in common parlor called

    insulin sensitizing.[the other word but equivalent is insulin resistance-by context]

    may be ,

    by increasing the expression of receptors on cell surface.

    or doing something towards the cascade of activities within the cell -tyrosine kinase-translocation of glut4 - glucose entry.-it is a long chain.unimportant for us for a moment .

    2]"lower the amount of sugar created by the liver,"


    this is from the glycogen to glucose path

    ..not gluconeogenesis.

    this is what is called closing a lid on liver--

    or some people calling it the prevention of glucose dumping.

    'neo genesis' is far away--

    stored glucose in liver is generally sufficient for 15 hours.


    neogenesis begins a bit earlier than full depletion of liver, before the completion of 15 hours.

    3]"decreasing the amount of sugar absorbed by the intestines."


    this is an activity similar to alpha glucosidase inhibition.--the drugs like acarbose- for instance.

    these three are the primary mechanisms or the most relevant mechanisms by which metformin acts .metformin may be having a lid on dietary excess protein conversion too.

    diabetes uk is second only to itself in english public health.

    but these are not the things patliputra is asking.

    that is insulin paradox.

    the paradox

    probably arises from

    the usage ="endogenous insulin does not work."

    this is a misunderstanding.

    endogenous insulin works but is insufficient due to the receptor insensitivity or whatever you may call it in a t2dm. probably long ago before the invention of receptor mechanism it was a it is just something to be explained.

    i had constructed the fish and net analogy [to be precise fish and angler] to explain why after insulin injection people are relieved of the excess glucose-

    that is something based on the so called diffusion principle with which

    we explain osmosis[kinetic theory of matter]

    that is =insulin touching the receptor is not by any facilitation--it is just random.

    thanks anyway for response.

    good luck

  • Indiacratus and mapalli, paradoxes are based on effects and not on causes. Nevertheless ,it was a good, meaningful and very informative discussion. After a very long time a discussion has taken place in a congenial and peaceful environment. Thanks to all members who participated as well as contributed. Hope it has helped the members in understanding different aspect of insulin metabolism. Thanks again .

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