Proinsulin
Encyclopedia
Proinsulin is the prohormone
precursor to insulin
made in the beta cell
s of the islets of Langerhans
, specialized regions of the pancreas
. In humans, proinsulin is encoded by the INS gene
.
s are oxidized. It is then transported to the Golgi apparatus
where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature insulin
. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide
. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds.
Prohormone
A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. The primary function of a prohormone is to enhance the strength of the hormone that already occurs in the...
precursor to insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat 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....
made in the beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s of the islets of Langerhans
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
, specialized regions of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. In humans, proinsulin is encoded by the INS gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Synthesis and post-translational modification
Proinsulin is synthesized in the endoplasmic reticulum, where it is folded and its disulfide bondDisulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
s are oxidized. It is then transported to the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat 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....
. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide
C-peptide
C-peptide is a protein that is produced in the body along with insulin. First preproinsulin is secreted with an A-chain, C-peptide, a B-chain, and a signal sequence. The signal sequence is cut off, leaving proinsulin...
. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds.
Immunogenicity
When insulin was originally purified from bovine or porcine pancreata, all the proinsulin was not fully removed. When some people used these insulins, the proinsulin may have caused the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin was injected. This can be described as an iatrogenic injury due to slight differences between the proinsulin of different species. Since the late 1970s, when highly-purified porcine insulin was introduced, and the level of insulin purity reached 99%, this ceased to be a significant clinical issue. It should also be noted that in respect of their influence on insulin pharmacokinetics, moderate concentrations of certain insulin antibodies may, in fact, be of positive advantage to all diabetics without endogenous insulin secretion (e.g. people with type 1 diabetes) because insulin binding antibodies effectively increase the insulin's clearance rate and distribution space and therefore helps to prolong its pharmacological and biological half lives.See also
- insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat 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....
- signal peptideSignal peptideA signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....
, signal peptide peptidaseSignal Peptide PeptidaseThe Signal Peptide Peptidase is an intramembrane aspartyl protease with the conserved active site motifs 'YD' and 'GxGD' in in adjacent transmembrane domains . Its sequences is highly conserved in different vertebrate species...
, preproinsulinPreproinsulinPreproinsulin is the primary translation product of the insulin gene. It is a peptide of 110 amino acids. Preproinsulin is a precursor processed by proteases to proinsulin by removal of the signal peptide and then to insulin by removal of the connecting peptide in order to be biologically... - proprotein convertase 1Proprotein convertase 1Proprotein convertase 1, also known as prohormone convertase, prohormone convertase 3, or neuroendocrine convertase 1 and often abbreviated as PC1/3 is an enzyme that in humans is encoded by the PCSK1 gene...
, proprotein convertase 2Proprotein convertase 2Proprotein convertase 2 also known as prohormone convertase 2 or neuroendocrine convertase 2 is a serine protease and proprotein convertase PC2, like proprotein convertase 1 , is an enzyme responsible for the first step in the maturation of many neuroendocrine peptides from their precursors, such...