What is Proinsulin?

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  • Written By: Geisha A. Legazpi
  • Edited By: Allegra J. Lingo
  • Last Modified Date: 09 November 2019
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Proinsulin is a protein molecule that serves as a precursor hormone, or prohormone, to insulin. Insulin is produced by the beta cells, which are pancreatic cells located in the islets of Langerhans, specifically through the cleavage of proinsulin by enzymes called protease. This cleavage process is important because measurement of the cleavage products can help doctors predict the actual amount of insulin production by the pancreas.

The insulin (INS) gene, located in chromosome 11, is first translated into a primary protein called preproinsulin, which is made up of 110 amino acids. After synthesis in the ribosomes, preproinsulin is transported to the endoplasmic reticulum. At one end of preproinsulin, there is a short chain of amino acids called signal peptide, which binds to a signal recognition particle (SRP). Binding of the signal peptide to the SRP allows intracellular transport of preproinsulin from the cytoplasm to the endoplasmic reticulum. When preproinsulin reaches the endoplasmic reticulum, an enzyme called signal peptide peptidase cleaves off the signal peptide, thereby turning preproinsulin to proinsulin.


Proinsulin is composed of 86 amino acids. It has three domains, or distinct peptide chains: alpha chain, beta chain, and C-peptide. Within the endoplasmic reticulum, enzymes called endopeptidases act on the whole prohormone to generate biologically active insulin. In particular, the endopeptidase called proprotein convertase 1 plays a significant role in the removal of the C-peptide in order to generate mature insulin. Another endopeptidase, called proprotein convertase 2, plays a minor role in the cleavage process, but has a greater role in the enzymatic production of glucagon, another hormone that regulates blood sugar.

Through the action of the proprotein convertase, mature insulin, which contains the alpha and beta chains, is generated. Mature insulin is made up of 51 amino acids. C-peptide, on the other hand, is composed of 31 amino acids. The remaining four amino acids are removed altogether and have no clinical significance.

The measurement of proinsulin in blood serum can be used to assess the status of the pancreatic beta cells. When its blood levels deviate from normal, dysfunction of either proinsulin secretion and/or processing is suspected. A deficiency or excess of this prohormone could give a clue as to why a person has diabetes, and how that person should be treated. For instance, people who have non-insulin-dependent diabetes mellitus (NIDDM) could have elevated proinsulin levels. The measurement of the proinsulin cleavage product called C-peptide is also useful in determining whether a person has type 1 or type 2 diabetes.


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Post 4

I remember my grandmother using insulin when I was a child. Back then, the synthetic insulin that is available now had not come out yet. Diabetes patients used insulin that came from animals.

I also remember my mom taking my grandmother to the hospital sometimes due to severe rashes that the insulin caused. I found out later, when I was in school that animal based insulin has way too much proinsulin in it, and that can cause adverse reactions in humans. Our body tends to resist and fight proinsulin that we don't produce ourselves.

Thankfully, this is not a concern anymore because the synthetic human insulin that we use today has very little proinsulin and people don't have these adverse reactions.

Post 3

@alisha- from what I know, people with diabetes have problems in the way their bodies respond to proinsulin. With your dad, for example, even though he has enough insulin, his body doesn't respond to the proinsulin properly, so it can't fully do its job.

I don't know much about studies, but I have a few friends with diabetes, and this is some of what I know from them.

Post 2

@alisha-- I know that there are several studies that found a correlation between Type 2 diabetes and the levels of proinsulin in blood in a fasting state. Researchers also feel that a certan proinsulin to insulin ratio is a sign of diabetes as well.

Despite these studies though, I don't think that there has been enough research to make any conclusions about diabetes and proinsulin. There is just a growing assumption that if doctors monitor proinsulin levels in people early on, they will be able to determine if someone is going to become a diabetes patient in the future or not.

We can also say that if we find ways for proinsulin and insulin control, we may be able to prevent type 2 diabetes this way in the future.

Post 1

I have diabetes patients in my family and I have heard a lot about insulin, but I didn't even know until now that there is a type of insulin called proinsulin.

My dad, for example, has Type 2 diabetes. His body produces enough insulin, but the insulin is morphed so it doesn't recognize the sugar molecules and use them.

I've always wondered what causes insulin to lose its original shape, leading to diabetes. After reading this article, I think it probably has to do with proinsulin and its cleavage process.

Are there any studies out there that have found a connection between proinsulin and diabetes?

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