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Insulin - Wikipedia. This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. INSAvailable structures. PDBOrtholog search: PDBe.
RCSBList of PDB id codes. A7. F, 1. AI0, 1. AIY, 1. B9. E, 1. BEN, 1. EFE, 1. EV3, 1. EV6, 1. EVR, 1. FU2, 1. FUB, 1. G7. A, 1. G7. B, 1. GUJ, 1.
HIQ, 1. HIS, 1. HIT, 1. HLS, 1. HTV, 1. HUI, 1. IOG, 1. IOH, 1. J7.
JCA, 1. JCO, 1. K3. M, 1. KMF, 1. LKQ, 1. LPH, 1. MHI, 1. MHJ, 1. MSO, 1. OS3, 1. OS4, 1.
Q4. V, 1. QIY, 1. QIZ, 1. QJ0, 1. RWE, 1.
SF1, 1. SJT, 1. SJU, 1. T0. C, 1. T1. K, 1. T1. P, 1. T1. Q, 1. TRZ, 1. TYL, 1. TYM, 1. UZ9, 1. VKT, 1. W8. P, 1. XDA, 1. XGL, 1.
XW7, 1. ZEG, 1. ZEH, 1. ZNJ, 2. AIY, 2. C8. Q, 2. C8. R, 2. CEU, 2. G5. 4, 2. G5. 6, 2. H6. 7, 2. HH4, 2. HHO, 2. HIU, 2. JMN, 2. JUM, 2. JUU, 2. JUV, 2.
JV1, 2. JZQ, 2. K9. K9. R, 2. KJJ, 2. KJU, 2. KQP, 2. KQQ, 2. KXK, 2. L1. Y, 2. L1. Z, 2. LGB, 2.
M1. D, 2. M1. E, 2. M2. M, 2. M2. N, 2. M2. O, 2. M2. P, 2. OLY, 2. OLZ, 2. OM0, 2.
OM1, 2. OMG, 2. OMH, 2. OMI, 2. QIU, 2. R3. R3. 5, 2. R3. 6, 2. RN5, 2. VJZ, 2. VK0, 2.
W4. 4, 2. WBY, 2. WC0, 2. WRU, 2. WRV, 2. WRW, 2. WRX, 2. WS0, 2. WS1, 2. WS4, 2. WS6, 2. WS7, 3. AIY, 3. BXQ, 3. E7. Y, 3. E7. Z, 3. EXX, 3. FQ9, 3. HYD, 3.
I3. Z, 3. I4. 0, 3. ILG, 3. INC, 3. IR0, 3. Q6. E, 3. ROV, 3. TT8, 3. U4. N, 3. UTQ, 3. UTS, 3. UTT, 3. V1. 9, 3. V1. G, 3. W1. 1, 3. W1. 2, 3.
W1. 3, 3. W7. Y, 3. W7. Z, 3. W8. 0, 3. ZI3, 3. ZQR, 3. ZS2, 3.
ZU1, 4. AIY, 4. AJX, 4. AJZ, 4. AK0, 4. AKJ, 4. EFX, 4. EWW, 4. EWX, 4. EWZ, 4. EX0, 4. EX1, 4. EXX, 4. EY1, 4. EY9, 4. EYD, 4. EYN, 4. EYP, 4. F0. N, 4. F0. O, 4.
F1. A, 4. F1. B, 4. F1. C, 4. F1. D, 4. F1. F, 4. F1. G, 4. F4. T, 4. F4. V, 4.
F5. 1, 4. F8. F, 4. FG3, 4. FKA, 4. GBC, 4. GBI, 4. GBK, 4. GBL, 4. GBN, 4. IUZ, 5. AIY, 2. LWZ, 3. JSD, 3. KQ6, 3. P2. X, 3. P3. 3, 1.
JK8, 2. MLI, 2. MPG, 2. MPI, 2. MVC, 2. MVD, 2. OMQ, 4. CXL, 4. CXN, 4. CY7, 4. IYD, 4. IYF, 4. NIB, 4. OGA, 4. P6.
Q5. Z, 4. RXW, 4. UNE, 4. UNG, 4. UNH, 4. XC4, 4. WDI, 4. Z7. Z7. 7, 4. Z7. 8, 2.
N2. W, 5. CO6, 5. ENA, 4. Y1. 9, 5. BQQ, 5. BOQ, 2. N2. V, 5. CNY, 5. CO9, 5. EN9, 4. Y1. A, 2.
N2. X, 5. BPO, 5. CO2, 5. BTS, 5. HYJ, 5. C0. DIdentifiers.
Aliases. INS, IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY1. External IDs. MGI: 9. Homolo. Gene: 1. 73. Gene. Cards: INSRNA expression pattern.
More reference expression data. Orthologs. Species. Human. Mouse. Entrez. Ensembl. Uni. Prot. Ref. Seq (m. RNA)Ref. Seq (protein)Location (UCSC)Chr 1. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucosefrom the blood into fat, liver and skeletal muscle cells.
It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism. Pancreatic beta cells (. When glucose concentrations in the blood are high, the pancreatic . This results in type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting. Instead there is an accumulation of amyloid in the pancreatic islets, which disrupts their anatomy and physiology. Insulin is still secreted into the blood in response to the blood glucose.
There are a variety of treatment regimens, none of which is entirely satisfactory. It is a dimer of an A- chain and a B- chain, which are linked together by disulfide bonds.
Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations.
Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. The insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels. A read- through gene, INS- IGF2, overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. In general, the A- boxes bind to Pdx.
E- boxes bind to Neuro. D, C- boxes bind to Maf. A, and c. AMP response elements to CREB. There are also silencers that inhibit transcription. Protein structure.
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 among species; it is also a hormone, but a secondary one.
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 insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules. This can cause injection amyloidosis, and prevents the storage of insulin for long periods. These stimuli include ingested protein and glucose in the blood produced from digested food.
If the carbohydrates include glucose, then that glucose will be absorbed into the bloodstream and blood glucose level will begin to rise. In target cells, insulin initiates a signal transduction, which has the effect of increasing glucose uptake and storage. Finally, insulin is degraded, terminating the response. Production and secretion are largely independent; prepared insulin is stored awaiting secretion.
Both C- peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale. In mammals, insulin is synthesized in the pancreas within the . One million to three million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas, which is primarily an exocrinegland. The endocrine portion accounts for only 2% of the total mass of the pancreas.
Within the islets of Langerhans, beta cells constitute 6. It is however first synthesized as a single polypeptide called preproinsulin in pancreatic .
Preproinsulin contains a 2. RER). The signal peptide is cleaved as the polypeptide is translocated into lumen of the RER, forming proinsulin. Transport to the TGN may take about 3. Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases (PC1 and PC2), as well as the exoprotease carboxypeptidase E. The cleavage sites are each located after a pair of basic residues (lysine- 6.
After cleavage of the C- peptide, these 2 pairs of basic residues are removed by the carboxypeptidase. The first- phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 1. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. Reduced first- phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes. These glucose transporters have a relatively low affinity for glucose, ensuring that the rate of glucose entry into the .
At low blood sugar levels very little glucose enters the . This means that the intracellular G- 6- P concentration remains proportional to the blood sugar concentration.