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C-peptide Emerging as Significant Factor in Nerve Recovery
3 January 2008
Because scientists often tend to dismiss what they don't fully understand, many of them used to think that C-peptide had no physiological function. But while it's true that C-peptide does nothing to lower blood sugar, recent research is finding that it might have a role in preventing diabetes complications.
C-peptide binds to cell surfaces and activates cell-signaling pathways, stimulating enzymes that usually have reduced activity in people with type 1.
Pancreas transplants promote reversal of diabetic neuropathy and stabilization of diabetic retinopathy, and both pancreas and islet transplants lead to reversal of diabetic nephropathy (kidney dysfunction). The assumption now is that the production of C-peptide associated with these procedures is behind the improvements.
C-peptide administration is also accompanied by increased blood flow in skeletal muscle, heart, and skin reduced glomerular hyperfiltration and urinary albumin secretion, and improved nerve function. This effect occurs in patients with type 1 diabetes, but not in healthy people.
In one study, nerve conduction speeds were measured in diabetic and healthy rats that were treated with either C-peptide or a placebo. The progressive decline in nerve conduction speed seen in placebo-treated rats was arrested when C-peptide treatment was started one week after onset of diabetes. The nerve conduction velocity also increased significantly when C-peptide was administered at five months after onset of diabetes.
In a three-month clinical trial involving patients with peripheral diabetic neuropathy, sensibility impairment improved after C-peptide treatment but then returned three months after treatment stopped. In another trial, sensibility impairment improved after three months of replacement C-peptide treatment.
Where C-peptide Comes From and What It Does
Discovered in 1967, C-peptide is a byproduct of insulin production that starts out as part of the proinsulin molecule. Proinsulin is the raw material for finished insulin. Made up of 86 amino acids, it's produced in the endoplasmic reticulum, deep within the beta cells of the pancreas. During the manufacturing process, the proinsulin molecule is folded into a tidy shape that can be neatly severed by enzymes into three parts: the A chain of the insulin molecule, the C-peptide molecule, and the B chain of the insulin molecule.
C-peptide, so named because it connects the A chain and B chain of insulin within the proinsulin molecule, is snipped out from the center of the proinsulin. C-peptide ends up with 31 amino acids, and four amino acids are removed altogether. The two ends of the proinsulin (the B chain, made up of 30 amino acids) and the A chain (made up of 21 amino acids) are connected to each other by two disulfide bonds, forming the finished insulin molecule of 51 amino acids.
For each insulin molecule produced, obviously, one C-peptide molecule is also produced. Measuring C-peptide, therefore, is a handy way to measure naturally produced insulin and to distinguish it from injected insulin, which has no C-peptide. (The C-peptide is removed when insulin is manufactured synthetically.)
What's Normal in People With Diabetes
In non-diabetics, a normal concentration of C-peptide is about 0.5 to 3.0 ng/ml. Even though C-peptide and insulin are produced at the same rate, the body's levels of the two are not identical because they leave the body at different speeds. Insulin is processed and eliminated mostly by the liver and has a half-life of about five minutes. C-peptide is removed by the kidneys and has a half-life of about thirty minutes. As a result, there is usually about five times as much C-peptide in the blood as insulin.
Because type 1 diabetes is caused by autoimmune destruction of beta cells, it is characterized by reduced levels of both insulin and C-peptide. Type 2 diabetes, in contrast, which begins with resistance to insulin, is initially associated with normal or even increased insulin and C-peptide levels. That's why a C-peptide test is often used to help distinguish between type 1 and type 2 diabetes. In a basic C-peptide test, fasting C-peptide levels are measured. Blood glucose levels are measured at the same time, and the two are correlated.
How a C-peptide Stimulation Test Works
In a C-peptide stimulation test, which is far less common than the fasting test, glucagon is administered to stimulate high blood sugar. In healthy people, this hyperglycemia would stimulate secretion of insulin molecules, each one associated with a C-peptide molecule. With type 1 diabetes, however, the pancreas is on the fritz. As a result, little insulin and C-peptide is secreted.
Conversely, C-peptide levels are increased in early type 2 diabetes because the pancreas is still going strong but the body's cells aren't able to use the insulin it produces. In people with type 2, C-peptide levels may also be monitored to determine whether the pancreas is burning out and insulin production is dropping, resulting in a need for insulin supplementation.
C-peptide and Medicare/Medicaid's Insulin Pump Policies
Medicare and Medicaid regulations require C-peptide testing as part of the qualification process for an insulin pump. C-peptide testing is also used to differentiate among different causes of low blood sugar, such as an insulin-producing pancreatic tumor called an insulinoma, which leads to excessive production of insulin and associated C-peptide.
The test can also identify an accidental or deliberate over-administration of insulin; because synthetic insulin does not contain C-peptide, C-peptide is low in persons with hypoglycemia due to overdose of insulin. C-peptide levels are also used to monitor beta cell function following surgical removal of all or part of the pancreas. Additionally, they are used to find out whether transplanted islet cells are producing insulin.
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Nice article, on the whole, but I strongly object to this characterization of people with diabetes (type 1 or 2) as unhealthy. I have had type 1 for 39 years now, and I am quite healthy.
"In healthy people, this hyperglycemia would stimulate secretion of insulin molecules, each one associated with a C-peptide molecule. With type 1 diabetes, however, the pancreas is on the fritz."
I think it would be much more accurate and respectful to phrase it as, "In people without diabetes, this hyperglycemia would stimulate secretion of insulin molecules..."
If a T1 diabetic wants to take c-peptides, does there exist a medication that can be taken? I know my c-peptide level is very low, less than 0.009µg/l! If such a medication does exist, do there exist any guidelines for how much one should take? Is it correct that animal insulins contain C-peptides? Can we then give ourselves c-peptides by using animal insulins rather than "human insulins"? PLEASE CONTINUE TO INFORM US OF ALL RESEARCH CONCERNING C-PEPTIDES! Thank you!
I would really appreciate answers to the questions in my above comment.
While the article is accurate about the levels of C-Peptide found in people with both types of diabetes, the author failed to mention that all insulins sold by Novo Nordisk, Eli Lilly & Co. and Sanofi-Aventis are completely stripped of C-peptide in the laboratory before they are even sold. E.coli or yeasts are injected with genetically modified insulin A and B peptide chains, but not the C peptide chain. This is one reason why the incidence of the incidence neuropathy in type 1 diabetes has risen steadily over the last 30 years in spite of better glycemic control overall. The drug companies are knowing making an incomplete product ... in fact, Eli Lilly has a strategy (see the company's quarterly earnings releases for details) to instead sell people with type 1 diabetes additional drugs to treat diabetes complications which might have been prevented if the insulin they sold was complete. Incidentally, prior to the 1982 introduction of synthetic "human" insulin, residual C-Peptides (albiet in miniscule quantities) were contained in the animal-sourced insulin sold to patients, although it is believed that the quantity was not sufficient to have any therapeutic impact.
Nowdays, most people with Type 1 diabetes ARE tested using C-peptide levels and antibody levels. Both are use to distinguish a diagnosis of Type 1 from Type 2 diabetes.
C-peptide should be mandatory for all Type 1 diabetics.
This is a very interesting article. Unfortunately, the information you give isn't enough for me to navigate to the original articles. Could you post citations, especially for the "three-month clinical trial involving patients with peripheral diabetic neuropathy"?
Where can I buy c-peptide ready for subcutaneous injection?
I've been following c-peptide research for several years. The research has looked very promising but the medical establishment has been largely ignoring it. Ever since insulin treatment was first introduced Drs. have been assuming that C-Peptide (created at the same time as insulin and as part of the insulin creation process) was just a "throw-away" substance. Surprise! The body doesn't make "throw-away" substances. When I ask researchers about it they say that it has to be proved that it's useful. I say, if it's part of what the body naturally produces in reaction to the presence of glucose, they should have to prove why it's NOT important. These are the same yahoos who said that formula was better than breast milk, that the appendix had no purpose (SURPRISE THEY JUST FOUND OUT IT DOES), and that margarine (jammed full of trans-fats) was healthier than butter. A properly functioning body generally doesn't make mistakes and we have to assume if it creates a substance it does so for a reason. I hope many of you will contact scientific journals, the Juvenile Diabetes Foundation, and anyone else you can think of to encourage them to fast-track research on supplementing with C-Peptide. The research to date shows it can have significant impact on preventing or reversing diabetic complications -- an absolutely critical issue for millions of Type 1 diabetics.
Why do they not develop C-peptide that can be either indegsted or injected by we Type 1's? Please post any available info on C-peptide or its development, we neuropathic Type 1.s do not have anything else to hope for.
Sweden based company creative peptide has started producing c peptide.Soon they are going to start to produce it at commercial scale.
Here's how to obtain c-peptide:
1. Find some people who have a compatible blood type.
2. Get a reliable mob surgeon.
3. Pay the people with compatible blood for a half a unit per week, and rotate each individual.
4. Have the mob surgeon put their blood into you.
America has the best health care system on earth!
For what its worth, the folks at Eli Lilly and Co. tested making rDNA proinsulin, which happens to include C-peptide. However, they pulled the plug on those studies in February 1988 when "the fact that unique efficacy in controlled multicenter studies was not demonstrated suggested that these pharmacological features were not translated into clinical benefit". They also claimed that there were 6 myocardial infarctions, including 2 deaths, although that was not proven to be caused by proinsulin per se, but being risk-averse, the company called it quits. Let the Swedes go with it, they'll make billions on something Lilly discarded a decade ago!
Diabetes Care. 1992 May; 15(5): 666-92
The C-peptide story is similar to the INGAP Peptide (Islet NeoGenesis Associated Protein, a peptide stimulating the genesis of Alfa & Beta cells from Stem cells alive but sleeping in pancreatic Islets).
Lilly in 2002, abandoned the level1 human trial on INGAP when they understud that the end of the BIG business of antidiabetic substances was coming. Procter&Gamble too decided to ends the level2 human trial on INGAP using the same words than Lilly on 2006 and now a new "noprofit" (kinexum.com) after less than 12 month says: "we will do INGAP on 2009" !!!! I'm not optimistic, do you think that THEY simply stay watching the end of the big business?
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