Tuesday, July 6, 2010

Insulin

Insulin is a hormone that is central to regulating the energy and glucose metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle.
Insulin stops the use of fat as an energy source. When insulin is absent, glucose is not taken up by body cells and the body begins to use fat as an energy source, for example, by transfer of lipids from
adipose tissue to the liver for mobilization as an energy source. As its level is a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.
When control of insulin levels fails,
diabetes mellitus will result. As a consequence, insulin is used medically to treat some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on external insulin (most commonly injected subcutaneously) for their survival because the hormone is no longer produced internally. Patients with Type 2 diabetes mellitus are insulin resistant, and because of such resistance, may suffer from a relative insulin deficiency. Some patients with Type 2 diabetes may eventually require insulin if other medications fail to control blood glucose levels adequately, though this is somewhat uncommon.
Insulin also influences other body functions, such as
vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and in particular benefits verbal memory.[2]
Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of 5808 Da. It is produced in the islets of Langerhans in the pancreas. The name comes from the Latin insula for "island". Insulin's structure varies slightly between species of animal. Insulin from animal sources differs somewhat in "strength" (in carbohydrate metabolism control effects) in humans because of those variations. Porcine (pig) insulin is especially close to the human version.
Regulation

There are several regulatory sequences in the promoter region of the human insulin gene, to which transcription factors bind.
In general, the A-boxes bind to Pdx1 factors, E-boxes bind to NeuroD, C-boxes bind to MafA and cAMP response elements to CREB.
There are also silencers that inhibit transcription.
Regulatory sequences and their transcription factors for the insulin gene.[5]
Regulatory sequence
binding transcription factors
ILPR
Par1
A5
Pdx1
negative regulatory element (NRE)[6]
glucocorticoid receptor, Oct1
Z (overlapping NRE and C2)
ISF
C2
Pax4, MafA(?)
E2
USF1/USF2
A3
Pdx1
CREB RE
-
CREB RE
CREB, CREM
A2
-
CAAT enhancer binding (CEB) (partly overlapping A2 and C1)
-
C1
-
E1
E2A, NeuroD1, HEB
A1
Pdx1
G1
-

Protein structure
Within vertebrates, the amino acid sequence of insulin is extremely well preserved. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C-peptide of proinsulin (discussed later), however, differs much more amongst species; it is also a hormone, but a secondary one.
Insulin is produced and stored in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer. The hexamer is an inactive form with long-term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer-monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons, however the monomer is a much faster reacting drug because diffusion rate is inversely related to particle size. A fast reacting drug means that insulin injections do not have to precede mealtimes by hours, which in turn gives diabetics more flexibility in their daily schedule.[7] Insulin can aggregate and form fibrillar interdigitated beta-sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods.[8]

No comments:

Post a Comment