6s34

<table><tr><td colspan='2'>[[6s34]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S34 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6S34 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6s34 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s34 OCA], [http://pdbe.org/6s34 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s34 RCSB], [http://www.ebi.ac.uk/pdbsum/6s34 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s34 ProSAT]</span></td></tr>

== Disease ==

[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:[http://omim.org/entry/176730 176730]].<ref>PMID:3470784</ref> <ref>PMID:2196279</ref> <ref>PMID:4019786</ref> <ref>PMID:1601997</ref> Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:[http://omim.org/entry/125852 125852]]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:18192540</ref> Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:[http://omim.org/entry/606176 606176]]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.<ref>PMID:17855560</ref> <ref>PMID:18162506</ref> Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:[http://omim.org/entry/613370 613370]]. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.<ref>PMID:18192540</ref> <ref>PMID:18162506</ref> <ref>PMID:20226046</ref>

== Function ==

[[http://www.uniprot.org/uniprot/INS_HUMAN INS_HUMAN]] Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

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== Publication Abstract from PubMed ==

Recently, the clinical proof of concept for the first ultra-long oral insulin was reported, showing efficacy and safety similar to subcutaneously administered insulin glargine. Here, we report the molecular engineering as well as biological and pharmacological properties of these insulin analogues. Molecules were designed to have ultra-long pharmacokinetic profile to minimize variability in plasma exposure. Elimination plasma half-life of ~20 h in dogs and ~70 h in man is achieved by a strong albumin binding, and by lowering the insulin receptor affinity 500-fold to slow down receptor mediated clearance. These insulin analogues still stimulate efficient glucose disposal in rats, pigs and dogs during constant intravenous infusion and euglycemic clamp conditions. The albumin binding facilitates initial high plasma exposure with a concomitant delay in distribution to peripheral tissues. This slow appearance in the periphery mediates an early transient hepato-centric insulin action and blunts hypoglycaemia in dogs in response to overdosing.

Molecular engineering of safe and efficacious oral basal insulin.,Hubalek F, Refsgaard HHF, Gram-Nielsen S, Madsen P, Nishimura E, Munzel M, Brand CL, Stidsen CE, Claussen CH, Wulff EM, Pridal L, Ribel U, Kildegaard J, Porsgaard T, Johansson E, Steensgaard DB, Hovgaard L, Glendorf T, Hansen BF, Jensen MK, Nielsen PK, Ludvigsen S, Rugh S, Garibay PW, Moore MC, Cherrington AD, Kjeldsen T Nat Commun. 2020 Jul 27;11(1):3746. doi: 10.1038/s41467-020-17487-9. PMID:32719315<ref>PMID:32719315</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Human]]

[[Category: Johansson, E]]

[[Category: Zinc free]]