For this reason "insulin insensitivity", or a decrease in insulin receptor signaling, leads to diabetes mellitus type 2 – the cells are unable to take up glucose, and the result is hyperglycemia (an increase in circulating glucose), and all the sequelae that result from diabetes $^{(1)}$


Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance. $^{(2)}$

So why don't we give people a medicine which just increases the number of receptors or increases the sensitivity of receptors? Isn't it illogical to give more of insulin for a deficit amount of receptors? So, what is the logic behind giving insulin?

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    $\begingroup$ Not all type-2 diabetics receive insulin. It depends on their HbA1C level in the beginning of treatment. See 2017 guidelines from the American Association of Clinical Endocrinologists and American College of Endocrinology. $\endgroup$ – Don_S Feb 28 '17 at 15:14
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    $\begingroup$ Can you add reference for the two quotes in the question? $\endgroup$ – another 'Homo sapien' Mar 1 '17 at 6:31

Isn't it illogical to give more of insulin for a deficit amount of receptors?

Seems like there is some confusion in the definition of type-2 DM itself. According to the American Diabetes Association:

If you have type 2 diabetes your body does not use insulin properly. This is called insulin resistance. At first, your pancreas makes extra insulin to make up for it. But, over time it isn't able to keep up and can't make enough insulin to keep your blood glucose at normal levels.

So the problem in type-1 DM and type-2 DM is quite same; both because of less insulin present than required, the difference being that in type-2 DM the cells need more insulin than normal. And that apparent deficiency of insulin is overcome by insulin injections. Also, the definition you cite doesn't say receptor deficiency anywhere, it just says decrease in receptor's response to insulin.

So why don't we give people a medicine which just increases the number of receptors or increases the sensitivity of receptors?

This is not quite possible yet. Increasing the number of receptors means increasing the gene expression for that receptor, something that is called 'upregulation'. Now, just to add, the cause of type-2 DM has been regarded to be downregulation of insulin receptors on cell surface by high concentration of insulin. See this article:

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell's sensitivity to the elevated hormone concentration.

Now, coming back to the main point, it is not yet possible to inject transcription factors in every cell of body so that more and more receptors can be produced. It is possible in vitro, but not in vivo yet. However, it is possible to inject something else instead of insulin which might have similar effects on the body, something known as insulin agonist. Researchers are already trying to create insulin agonists, but haven't achieved much success. See this paper for example, in which they talk about a peptide S961. The problem here is that most of the molecules synthesized act as both agonist and antagonist based on different concentrations. That is why this field has not seen much success.

EDIT: As mentioned by @Don_S in comments, some drugs reportedly do increase insulin sensitivity and number of receptors in cells. Though they have indirect mechanisms for this, unlike insulin itself, but this works too (at least in vitro). One of them, thiazolidinediones, activates a nuclear receptor PPAR $\gamma$, which in turn increases transcription of proteins involved in glucose and lipid metabolism and energy balance. Another drug, pioglitazone, works even in vivo and has been suggested to work by activating receptor kinases and thus increase insulin sensitivity.

Thus, in future, it is very likely that type-2 DM patients would get prescriptions of such drugs instead of insulin injections, but not until there are more such drugs available and at an affordable cost.


  1. Type 2 — American Diabetes Association

  2. Downregulation and upregulation — Wikipedia

  3. Knudsen L, Hansen BF, Jensen P, Pedersen TÅ, Vestergaard K, Schäffer L, et al. (2012) Agonism and Antagonism at the Insulin Receptor. PLoS ONE 7(12): e51972. doi:10.1371/journal.pone.0051972

  4. Hauner H. The mode of action of thiazolidinediones. Diabetes Metab. Res. Rev. 2002;18(Suppl. 2):S10–S15. doi: 10.1002/dmrr.249.

  5. Kobayashi, M, Iwanishi, M, Egawa, K et al, Pioglitazone increases insulin sensitivity by activating kinase of insulin receptors. Diabetes. 1992;41:476–483.

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  • $\begingroup$ Somewhere I have read that insulin induces more receptor formation. $\endgroup$ – JM97 Feb 28 '17 at 15:26
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    $\begingroup$ @JM97 if it did so, then how would insulin resistance develop? Upregulation would mean increased sensitivity of cells towards insulin, but this quite the opposite of what happens. $\endgroup$ – another 'Homo sapien' Feb 28 '17 at 15:33
  • $\begingroup$ then why do insulin overdose occurs? $\endgroup$ – JM97 Feb 28 '17 at 16:06
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    $\begingroup$ OP: "So why don't we give people a medicine which just increases the number of receptors or increases the sensitivity of receptors?" - "This is not quite possible yet." Actually, it is. There is a group of anti-diabetic drugs called Thiazolidinediones which is said to increase the sensitivity of body cells to insulin. This rather old study (from when these drugs were new...) indicates that these drugs activate insulin receptor kinase. This is not glucose receptors upregulation, but it is an increase in the response to insulin. $\endgroup$ – Don_S Feb 28 '17 at 17:04
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    $\begingroup$ @Don_S thanks a ton for the references, added them in the answer :) $\endgroup$ – another 'Homo sapien' Feb 28 '17 at 17:24

This is true for the beginning of the disease. As a reaction to the reduced sensitivity of the cells in the body to insulin (and thus less uptake of glucose from the blood and a resulting hyperglycemia) the body produces more and more insulin to cope with this problem.

At some point the insulin producing beta cells cannot increase the production anymore and due to the insulin resistance this amount is not enough anymore. At this point insulin needs to be supplied to the body to ensure normal function and to combat hyperglycemia. See this figure for a schematic overview (from here):

enter image description here

For more details see this paper:

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Insulin is a "last resort" treatment for people with Type 2 diabetes—partly due to the unpleasantness of injections, but partly due to the fact that high insulin levels can worsen insulin resistance.

People with Type 2 diabetes are generally started on Metformin and/or advised on diet and exercise, and progress to other oral medication, before insulin is considered. However, the oral drugs can have significant side-effects, and since Type 2 diabetes is progressive, insulin can eventually become necessary.

That said, injected insulin carries the risk of hypoglycaemia (low blood sugar), and starting insulin treatment early, before pancreatic insulin production has been severely impacted, can help reduce this risk, as the pancreas can play more of a role in keeping blood sugars stable.

So, the simple answer is: insulin treatment is used because it works; reducing insulin resistance is preferable, but current drugs can only do this to a limited extent.

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