- Stimulation of DNA translation
- Increased lipid synthesis
- Stimulation of Na+,K+, and Pitransport into cells
Insulin is therefore seen as a hormone-promoting anabolism rather than catabolism,
since it promotes the synthesis of glycogen, proteins, and lipids. It is quite clear from
the preceding list of insulin actions on metabolic functions that the hormone has a much
broader biochemical role than the regulation of carbohydrate metabolism and removal
of free circulating glucose. In the absence of insulin, therefore, there are profound
changes in the entire metabolic pattern. Since carbohydrate, the principal nutrient in
most diets, cannot be utilized properly, the energy requirements of the diabetic organ-
ism must be met in other ways. One of these is an increased gluconeogenesis from
protein, with the consumption of body tissues; there is also an increased excretion of
nitrogen and diminished protein synthesis (therefore, the patient’s body wastes despite
the high glucose in the bloodstream—“starvation in the midst of plenty”). The glucose
produced in such a tedious and harmful way is also excreted and wasted. Lipolysis
occurs, resulting in lipemia (an excess of circulating lipids), and ketone bodies such as
acetoacetate and acetone are produced excessively.
In recent years, tremendous progress has been achieved in the elucidation of the cel-
lular and molecular mechanisms of insulin action. The acute cellular action of insulin
is initiated by rapid clustering of occupied receptors on the cell surface. Within three
minutes, a redistribution of glucose transporters from the cytoplasm to the plasma
membrane can be measured; lipolysis is also increased.
5.20.1.2 Insulin Preparations and Insulin-like Drugs
Insulin Preparations.Since diabetes mellitus is a defect of one or more of insulin
production, secretion, or action, the administration of insulin replacement as a treatment
for diabetes in the 1920s was a landmark discovery. Historically, most commercial
insulin came from either bovine or porcine sources. Beef insulin differs from human
insulin by three amino acid substitutions; pork insulin differs by only one residue. For
many years, standard insulin preparations were 70% beef and 30% porcine. However,
the biosynthesis of human insulin has now displaced the animal insulins, especially
bovine insulin which was more antigenic. Mass production of human insulin by recom-
binant DNA methods is achieved by inserting the human proinsulin gene into either
E. colior yeast and treating the resulting proinsulin to yield the human insulin molecule.
Insulin preparations may be divided into four major types:
- Ultra-short-acting insulin, very rapid onset, short duration (e.g., lispro insulin)
- Short-acting insulin, rapid onset of action (e.g., regular insulin)
- Intermediate-acting insulin (e.g., NPH or isophane, lente, or zinc insulin)
- Long-acting insulin, slow onset of action (e.g., ultralente insulin)
The short-acting insulins are dispensed with the insulin molecules in solution, thereby
enabling a rapid onset of action. The intermediate- and long-acting insulins are dis-
pensed as turbid suspensions such that mobilization of the insulin molecule from the
366 MEDICINAL CHEMISTRY