Insulin – Pharmacology, Therapeutic Regimens, and Principles of Intensive Insulin Therapy

Since the introduction    of insulin analogs in 1996, insulin therapy options for type 1 and type 2 diabetics have expanded. Insulin therapies are now able to more closely mimic physiologic insulin secretion and thus achieve better glycemic control in patients with diabetes. This chapter reviews the pharmacology of available insulins, types of insulin regimens, and principles of dosage selection and adjustment, and provides an overview of insulin pump therapy. For complete coverage of this and related aspects of Endocrinology, please visit our FREE web-book,

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In 1922, Canadian researchers were the first to demonstrate a physiologic response to injected animal insulin in a patient with type 1 diabetes. In 1955, insulin was the first protein to be fully sequenced. The insulin molecule consists of 51 amino acids arranged in two chains, an A chain (21 amino acids) and B chain (30 amino acids) that are linked by two disulfide bonds (1) (Figure 1). Proinsulin is the insulin precursor that is transported to the Golgi apparatus of the beta cell where it is processed and packaged into granules. Proinsulin, a single-chain 86 amino acid peptide, is cleaved into insulin and C-peptide (a connecting peptide); both are secreted in portions from the beta cell upon stimulation from glucose and other insulin. While C-peptide has no known physiologic function, it can be measured to provide an estimate of endogenous insulin secretion.

Figure 1:
Figure 1:
Insulin Structure

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With the availability of human insulin by recombinant DNA technology in the 1980s, use of animal insulin declined dramatically. Beef insulin, beef-pork and pork insulin are no longer commercially available in the United States. The United States FDA may allow for personal importation of beef or pork insulin from a foreign country if a patient cannot be treated with human insulin (2). Beef insulin differs from human insulin by 3 amino acids and pork insulin differs by one amino acid (1).

Currently, in the United States, insulins used are either human insulin and/or analogs of human insulin. The recombinant DNA technique for human insulin involves insertion of the human proinsulin gene into either Saccharomyces cerevisiae (baker’s yeast) or a non-pathogenic laboratory strain of Escherichia coli (E coli) which serve as the production organism. Human insulin is then isolated and purified (3-11).

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Recombinant DNA technology has allowed for the development and production of analogs to human insulin. With analogs, the insulin molecule structure is modified slightly to alter the pharmacokinetic properties of insulin, primarily affecting the absorption of the drug from the subcutaneous tissue. The B26-B30 region of the insulin molecule is not critical for insulin receptor recognition and it is in this region that amino acids are generally substituted (12). Thus, the insulin analogs are still recognized by and bind to the insulin receptor. The structures of three rapid-acting insulin analogs are shown in Figure 2 (insulin  and the structures of three long-acting insulin analogs are shown in Figure 3 (insulin


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