Immature and Mature Insulin

Majid Ali, M.D.

Insulin is produced as a prehormone and is matured through a series of enzyme (catalystic) reactions. The evolutionary wisdom in this design goes unrecognized. I explain this with an analogy. What would happen if all the gasoline in an automobile engine was suddenly ignited? A massive explosion. Engineers designed a carburetor to assure a steady mixing of gasoline with air and a highly controlled ignition of the mixture. One of Nature’s master metabolic strokes is the creation of a prehormone-hormone design for slow and steady production of the mature hormone.

Insulin is composed of 51 amino acid units strung into a chain with a molecular weight of 5808 daltons. It is produced in specialized cells in the pancreas called the islet cells of Langerhan. The word insulin is derived from the Latin insula for “island”. Insulin is derived from a precursor called proinsulin. The human insulin gene has several regulatory components (sequences) in a region of its structure called the promoter region. The insulin receptor embedded in cell membranes is about sixty times as large in size as insulin.

Insulin is derived from a prohormone called proinsulin, which is synthesized in a compartment of beta cells called the endoplasmic reticulum. Proinsulin is folded and its disulfide bonds are oxidized. Next it is transported to another compartment called the Golgi apparatus, where it is packaged into secretory vesicles. A series of enzymes called proteases work on the prohormone to form mature insulin, which has 39 fewer amino acids. Insulin C-peptide is formed when four amino acids are removed.

In health, insulin is a guardian angel of life; in excess, it is a molecular monster. This is a crucial point since nearly all cases of Type 2 diabetes start out with excess insulin (hyperinsulinism). Diabetes is primarily misunderstood and mismanaged because insulin toxicity is not taught nor recognized in clinical guidelines of the ADA. Nearly all untruths and outright falsehoods about the cause of diabetes and most clinical errors in caring for people with insulin disorders can be traced to the ADA’s neglect of the long-term dangers of insulin toxicity. “Eat whatever you want, and we will cover it with insulin” was the advice that many of my patients received. Insulin toxicity that occurs almost invariably with this approach was not mentioned.


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