Insulin

Insulin is a polypeptide hormone produced by the beta cells of the pancreatic islets of Langerhans. It plays a central role in regulating blood glucose levels, generally keeping it within narrow defined limits (3.5-8.0 mmol T1), irrespective of the nutritional status of the animal. It also has a profound effect on the metabolism of proteins and lipids and displays some mitogenic activity. The latter is particularly evident in in vitro studies and at high insulin concentrations. Some of these mitogenic effects are likely mediated via the IGF-1 receptor, and their physiological relevance is questionable.

Although many cells in the body express the insulin receptor, its most important targets are skeletal muscle fibres, hepatocytes and adipocytes, where it often antagonizes the effects of

Pharmaceutical biotechnology: concepts and applications Gary Walsh © 2007 John Wiley & Sons, Ltd ISBN 978 0 470 01244 4 (HB) 978 0 470 01245 1 (PB)

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 reflects the relative rates of these hormones present in the plasma

Metabolic pathway

Target tissue

Effect of insulin

Effect of glucagon

Glycogen synthesis

Liver

T

i

Glycogen degradation

Liver

i

T

Gluconeogenesis

Liver

i

T

Glycogen synthesis

Muscle

T

-

Glycogen degradation

Muscle

-

-

Fatty acid synthesis

Adipose

T

i

Fatty acid degradation

Adipose

i

T

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 glycogen 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.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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