The discovery of insulin, in 1922, was a breakthrough in the treatment of diabetes and it produced a remarkable increase in the life expectancy of diabetic patients. Animal-derived insulins have been used to treat people with diabetes since insulin was first discovered and continuously subjected to various purification technologies. In 1973, Novo produced a purer type of insulin, called monocomponent insulin. This set a new standard in purity. In 1982, Human Monocomponent was the world's first insulin preparation identical to human insulin. It was actually pig insulin, modified by enzymes, to appear identical to human insulin.
When Novo tried to introduce monocomponent insulin into the USA, Lilly fought back with 'human' Humulin insulin. Before Humulin insulin became available, insulin had been produced from animal sources, pigs and cows. It is believed by some that the animal insulin provided the diabetic with better awareness of hypos, and it is certainly true that the long-acting animal insulin such as Ultralente are longer-acting than their 'human' equivalents. The fact that both pig and cow differ from human insulin by certain amino acids (1 in pig and 3 in cow) has lead the majority of physicians to recommend 'human' insulin. 'Animal' insulin became increasingly hard to find, particularly in the USA (see This Little Piggy Left the Market).
In the late 1990s Eli Lilly developed Lispro, brand name Humalog. This was approved for prescription use in the UK and the US by 1996. This insulin has a shorter activity curve than Regular. This means it can be injected closer to the meal time, even after it. Studies have shown that it does not improve control as measured by long-term indicators (Hba1c), but that it does decrease the number of hypos. Glargine, brand name Lantus, was approved for use in the US in 2004. It has become widely touted as better than other long-acting insulins because it has a plateau effect on glucose control that lasts for approximately 24 hours. Some people find it acts a little shorter (and some doctors don't believe that's possible!) So there you have it - the short and sweet version of the history of insulin. I strongly suggest anyone who wishes to fill the spaces between the discovery in 1922 and present day to pickup The Discovery of Insulin (Michael Bliss). I welcome all comments to fill-in the pivotal details I've failed to include.
1. With the end of Porcine and Beef Derived Insulin, an end to the availability of C-peptide resulted. This loss is monumental for all people who use Insulin because of the following reasons as reported from the Proceedings of the National Academy of Sciences of the United States of America(PNAS),
In Vol. 96, Issue 23, 13318-13323, November 9, 1999, It states that C-peptide which was thought of having no real significance other than its role in pro-insulin and as a bio-marker for insulin availability began to show tissue and membrane protective qualities in people with T1DM(Type 1 Diabetes Mellitus).
Since this is of extreme importance and value to those in the T1DM Community whose Lives are or will be affected by Complications related to Diabetes, I will quote a part of what was "discovered" in the study.
"Since the discovery in 1967 of the mode of insulin biosynthesis (1, 2), it has generally been held that C-peptide, the connecting segment of pro-insulin, does not possess biological activity of its own. However, recently, several studies have raised doubts concerning this view. Short-term C-peptide replacement in animals with experimental diabetes and in patients with type 1 diabetes is accompanied by improved renal function (3, 4), augmented glucose utilization (3, 5, 6), increased blood flow in muscle and skin (5, 7), and improved autonomic nerve function (8). Prolonged C-peptide administration (1-3 months) in type 1 diabetes patients results in improvements of renal function and amelioration of autonomic and sensory nerve dysfunction (9, 10). In vitro studies have confirmed that C-peptide stimulates glucose transport in skeletal muscle and that this effect is mediated via pathways other than the insulin receptor (11). C-peptide also improves RBC deformability in type 1 diabetes patients (12). The different effects correlate with stimulation of both Na+,K+-ATPase and endothelial NO synthase activities by C-peptide [refs. 13-15; and T. Kunt (Johannes Gutenberg University Hospital, Mainz, Germany), personal communication]. In renal tubular segments, this stimulation is compatible with activation of a G protein-coupled receptor with subsequent activation of Ca2+-dependent intracellular signaling pathways (13)".
It is my feeling and a number of Physicians that I have recently spoken with, that T1DM is more than a Disease of Glucose Numbers. Yes, having high elevations in Glucose can hasten Complications, but even with "good numbers", they can still occur because of the Nature of this Illness.
Here then are the concluding remarks that show that C-peptide has a prominent role of importance to play in the prevention or/and delay of T1DM related Complications:
"The progressive destruction of the -cells of the pancreas that is characteristic of diabetes mellitus type 1 results in deficiency and eventually total lack of both circulating insulin and C-peptide. Insulin replacement therapy, even when carefully adjusted with multiple daily injections, cannot prevent the development of long-term complications, involving kidneys, nerves, and eyes (38). The present study shows that C-peptide binds specifically to cell membranes. This observation, coupled with previous findings of physiological effects (3-11) relating to Na+,K+-ATPase (13-15) and endothelial NO synthase activities (T. Kunt, personal communication), provides a basis for the hypothesis that C-peptide is a biologically active peptide hormone whose effects are targeted to the micro-circulation of renal, nerve, and retinal tissues. Whether C-peptide, when administered together with insulin to type 1 diabetes patients on a long-term basis can retard or prevent the development of micro-vascular complications will henceforth be an important question to address".
Posted at 10:35AM on May 18th 2007 by BetterCell