User:Karisma Moll/Sandbox 1

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 51: Line 51:
DPP-IV binds and degrades GLP-1 <scene name='10/1037489/Glp1_peptide__scissile_bond/3'>(cleaving at the penultimate position)</scene> resulting in heightened blood glucose levels. Insufficient GLP-1 production or signaling in response to meal intake is clinically associated with T2DM and morbidity. Since GLP-1 is a potent regulator of blood glucose levels, and DPP-IV antagonistically regulates GLP-1, this makes DPP-IV inhibitors an excellent candidate for pharmacological therapeutics for T2DM. <ref name="Gilbert">PMID:32308645</ref>
DPP-IV binds and degrades GLP-1 <scene name='10/1037489/Glp1_peptide__scissile_bond/3'>(cleaving at the penultimate position)</scene> resulting in heightened blood glucose levels. Insufficient GLP-1 production or signaling in response to meal intake is clinically associated with T2DM and morbidity. Since GLP-1 is a potent regulator of blood glucose levels, and DPP-IV antagonistically regulates GLP-1, this makes DPP-IV inhibitors an excellent candidate for pharmacological therapeutics for T2DM. <ref name="Gilbert">PMID:32308645</ref>
 +
Recent studies are demonstrating connections between regulation of Caveolin-1 (Cav-1) and subsequent GLP-1 action. Cav-1, the principal protein of caveolae, is an integral membrane protein that co-localizes with GLP-1R to regulate receptor trafficking and control the assembly of signaling molecules. DIRECT INTERACTION OF Cav-1 with GLP-1R is required for trafficking and regulation. This interaction occurs with the binding motif in the second intracellular loop of GLP-1R. Two residues in particular, Y250 and Y252, were proved to be crucial in the binding of Cav-1. Cav-1 also binds to Ser630 of the DPP-IV catalytic triad, regulating the activity of DPP-IV and its inhibitors. (INSERT REFERENCE)

Revision as of 00:19, 24 April 2024

Structure and Function of Dipeptidyl Peptidase IV (DPP-IV) in Humans

PDB 6B1E for DPP-IV in complex with Vildagliptin

Drag the structure with the mouse to rotate

References

  1. Ahrén B. DPP-4 Inhibition and the Path to Clinical Proof. Front Endocrinol (Lausanne). 2019 Jun 19;10:376. PMID:31275243 doi:10.3389/fendo.2019.00376
  2. Khalse M, Bhargava A. A Review on Cardiovascular Outcome Studies of Dipeptidyl Peptidase-4 Inhibitors. Indian J Endocrinol Metab. 2018 Sep-Oct;22(5):689-695. PMID:30294582 doi:10.4103/ijem.IJEM_104_18
  3. Hocher B, Reichetzeder C, Alter ML. Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research. Kidney Blood Press Res. 2012;36(1):65-84. PMID:22947920 doi:10.1159/000339028
  4. Zhong J, Rajagopalan S. Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease. Front Immunol. 2015 Sep 25;6:477. PMID:26441982 doi:10.3389/fimmu.2015.00477
  5. Sharma A, Ren X, Zhang H, Pandey GN. Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: A postmortem study. Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jan 10;112:110428. PMID:34411658 doi:10.1016/j.pnpbp.2021.110428
  6. Ntafam CN, Beutler BD, Harris RD. Incarcerated gravid uterus: A rare but potentially devastating obstetric complication. Radiol Case Rep. 2022 Mar 10;17(5):1583-1586. PMID:35309386 doi:10.1016/j.radcr.2022.02.034
  7. Abbott CA, McCaughan GW, Levy MT, Church WB, Gorrell MD. Binding to human dipeptidyl peptidase IV by adenosine deaminase and antibodies that inhibit ligand binding involves overlapping, discontinuous sites on a predicted beta propeller domain. Eur J Biochem. 1999 Dec;266(3):798-810. PMID:10583373 doi:10.1046/j.1432-1327.1999.00902.x
  8. Dobers J, Grams S, Reutter W, Fan H. Roles of cysteines in rat dipeptidyl peptidase IV/CD26 in processing and proteolytic activity. Eur J Biochem. 2000 Aug;267(16):5093-100. PMID:10931192 doi:10.1046/j.1432-1327.2000.01571.x
  9. Kim BR, Kim HY, Choi I, Kim JB, Jin CH, Han AR. DPP-IV Inhibitory Potentials of Flavonol Glycosides Isolated from the Seeds of Lens culinaris: In Vitro and Molecular Docking Analyses. Molecules. 2018 Aug 10;23(8):1998. PMID:30103438 doi:10.3390/molecules23081998
  10. Hiramatsu H, Kyono K, Higashiyama Y, Fukushima C, Shima H, Sugiyama S, Inaka K, Yamamoto A, Shimizu R. The structure and function of human dipeptidyl peptidase IV, possessing a unique eight-bladed beta-propeller fold. Biochem Biophys Res Commun. 2003 Mar 21;302(4):849-54. PMID:12646248
  11. Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna J Med. 2020 Oct 13;10(4):174-188. PMID:33437689 doi:10.4103/ajm.ajm_53_20
  12. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. PMID:17928588 doi:10.1152/physrev.00034.2006
  13. Gilbert MP, Pratley RE. GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials. Front Endocrinol (Lausanne). 2020 Apr 3;11:178. PMID:32308645 doi:10.3389/fendo.2020.00178

Student Contributors

  • Karisma Moll
  • Merritt Jugo
  • Sam Magnabosco

Proteopedia Page Contributors and Editors (what is this?)

Karisma Moll

Personal tools