Therapeutic hormones - Pharmaceutical Biotechnology: Concepts and Aapplications - page 294

Table 11.1 Some metabolic effects of insulin. These effects are generally countered by other
hormones (glucagon and, in some cases, adrenaline). Hence, the overall effect noted often
refl ects the relative rates of these hormones present in the plasma

Metabolic pathway Target tissue Effect of insulin Effect of glucagon

Glycogen synthesis Liver ↑ ↓

Glycogen degradation Liver ↓ ↑

Gluconeogenesis Liver ↓ ↑

↑

Glycogen synthesis Muscle -

Glycogen degradation Muscle - -

Fatty acid synthesis Adipose ↑ ↓

Fatty acid degradation Adipose ↓ ↑

glucagon (Table 11.1). The most potent known stimulus of pancreatic insulin release is an increase
in blood glucose levels, often occurring after meal times. Insulin orchestrates a suitable metabolic
response to the absorption of glucose and other nutrients in a number of ways:

• it stimulates glucose transport (and transport of amino acids, K ions and other nutrients) into

cells, thus reducing their blood concentration;

• it stimulates (or helps to stimulate) intracellular biosynthetic (anabolic) pathways, such as glyco-

gen synthesis (Table 11.1), which helps to convert the nutrients into a storage form in the cells;

• it inhibits (or helps to inhibit) catabolic pathways, such as glycogenolysis;

• it stimulates protein and DNA synthesis (which underlines insulin's growth-promoting activity).

In general, insulin achieves such metabolic control by inducing the dephosphorylation of several
key regulatory enzymes in mainline catabolic or anabolic pathways. This inhibits the former and
stimulates the latter pathway types. These effects are often opposed by other hormones, notably
glucagon and adrenaline. Thus, when blood glucose concentrations decrease (e.g. during fasting),
insulin levels decrease and the (largely catabolic) effects of glucagon become more prominent.
Insulin also induces its characteristic effects by altering the level of transcription of various genes,
many of which code for metabolic enzymes. Another gene upregulated by insulin is that of the
integral membrane glucose transporter.

11.2.1 Diabetes mellitus

Failure of the body to synthesize suffi cient insulin results in the development of insulin-dependent
diabetes mellitus (IDDM). This is also known as type-1 diabetes or juvenile-onset diabetes.
IDDM is caused by T-cell-mediated autoimmune destruction of the insulin-producing β-pancreatic
islet cells in genetically predisposed individuals. This is probably due to the expression of a 'super
antigen' on the surface of the β-cells in such individuals, although the molecular detail of what extent
factors trigger onset of the -cell destruction remain to be elucidated. IDDM may, however, be control-

led by parenteral administration of exogenous insulin preparations, usually by regular s.c. injection.

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