Insulin Basics

00:01 Let’s have a look at insulin synthesis.

00:04 Insulin is synthesized as a 110 amino acid long preproinsulin, composed of a signal peptide, depicted in orange, a B-chain in blue, the connecting peptide in yellow, which is a C-peptide to be exact and lastly the red part, which is the A-chain.

00:23 The signal peptide is later cleaved off, resulting in the formation of proinsulin.

00:29 Within the endoplasmic reticulum, three disulfide bonds are formed between cysteine residues.

00:36 Proinsulin is then transported to the Golgi apparatus, where the C-peptide is cleaved off. This process converts proinsulin into mature insulin, which consists of the B and A chains only.

00:51 Keep in mind that C-peptide is only produced during endogenous insulin production. Therefore, in the case of exogenous insulin, which is taken by diabetics, no C-peptide will be found in the blood.

01:06 Exogenous insulin is typically manufactured in recombinant DNA technology using Escherichia coli.

01:13 This type of insulin does not contain C-peptide, this allows the differentiation between true endogenous and false exogenously produced hypoglycemia.

01:25 Insulin.

01:28 Insulin forms usually of what glucagon is.

01:33 It's formed also in the islet and specifically in the beta cells.

01:38 It is also a peptide hormone similar to glucagon.

01:43 It is clear about 50% by the first path.

01:48 This is an important process because again it's going to mean that insulin is not around in the circulation very long.

01:56 In fact it's half life is only 3 to 8 minutes.

02:03 Importantly what we have produced at the same time as the peptide hormone insulin is something called C-peptide.

02:14 Don't get this mixed up with C reactive peptide.

02:17 This is just C-peptide.

02:20 C-peptide is when passed through this first pass system in a slower time frame.

02:29 Therefore, it has a longer half life.

02:32 About 35 minutes.

02:35 If you compare 35 minutes half life versus a 3 to 8 minute half life, you can see that C-peptide stays in the circulation longer.

02:45 How is that useful for you clinically.

02:47 How useful is that, you can use C-peptide if you measured in the blood as an index for how much insulin is being secreted.

02:59 Because insulin is not going to be around long enough to really measure it's concentrations.

03:04 But if you measure C-peptide, you know it's produced in a 1 to 1 ratio.

03:09 Therefore, if C-peptides goes up, insulin has to go up and vice versa.

03:16 You can see how this break down of this process works.

03:19 If you see this polypeptide being formed.

03:22 And there's a cleave that happens, that forms C-peptide and insulin.

03:28 So they'll be making this preformed proinsulin peptide.

03:34 You cleave a certain spot, leaving C-peptide and insulin as your two different secretory substrates.