Therapeutic hormones - Pharmaceutical Biotechnology: Concepts and Aapplications - page 298

Table 11.2 Selected genes whose rate of transcription is altered by binding of insulin to
its receptor. In virtually all instances, the ultimate effect is to promote anabolic events
characteristic of insulin action. Two-dimensional gel electrophoresis has also pinpointed
dozens of proteins of unknown function whose cellular level is altered by insulin

Insulin effect (↑ or ↓
in transcription rate) Protein class Gene product

Integral membrane Insulin receptor ↑↓

proteins GH receptor ↑

Glucose transporters ↑

Enzymes Fatty acid synthetase ↑

Glutamine synthetase ↑↓

Pyruvate kinase ↑

Fructose 1,6-bis-phosphatase ↓

Phosphoenolpyruvate
carboxykinase

↓

Glucokinase ↑

Hormones IGF-1 ↑

Glucagon ↓

GH ↓

Transcription factors C-Myc ↑

C-Fos ↑

egr-1 ↑

• Immunogenicity . Bovine insulin differs from human insulin by three amino acids and it elicits

an immunological response in humans. This can trigger long-term complications, including
insulin resistance (as anti-insulin antibodies neutralize some of the administered products).
The presence of these antibodies can also affect the pharmacokinetic profi le of the drug, as
antibody-bound insulin molecules are largely resistant to the normal insulin degradative proc-
ess. Porcine insulin, differs from human insulin by only a single amino acid (residue 30 of the
B-chain; threonine in humans, alanine in pigs) and is essentially non-immunogenic in humans.
However, many of the porcine insulin contaminants (including porcine proinsulin) are immu-
nogenic in humans.

• Availability . Some 170 million people suffer from diabetes worldwide, a fi gure projected to

double by 2030. Insulin administration is essential to the survival of those with type-1 (in-
sulin-dependent) diabetes, and is required to control the progression of a minority of those
with (the more common) insulin-independent type-2 diabetes. The annual insulin requirement
has surpassed 5000 kg and continues to grow, prompting concern of an insulin shortfall from
slaughterhouse sources.

Such issues and concerns underpinned the development of recombinant human insulin products,
now routinely used in the management of diabetes.