1 / 14

Heparin Sulfate in Normal Islets ( Alcina blue and Histochemistry staining)

Heparin Sulfate in Normal Islets ( Alcina blue and Histochemistry staining). Invading mononuclear cells of NOD mice express heparanase. NOD DM Prevention with inhibitor heparanase.

shubha
Download Presentation

Heparin Sulfate in Normal Islets ( Alcina blue and Histochemistry staining)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Heparin Sulfate in Normal Islets (Alcina blue and Histochemistry staining) Invading mononuclear cells of NOD mice express heparanase NOD DM Prevention with inhibitor heparanase Ziokowski..Simeonovic: Heparan sulfate and heparanase play key roles in mouse beta cell survival and autoimmune diabetes JCI 122:132-141, 2012

  2. Insulin Secretory Granules Multigranular Body Storage Pool Degradation Complex Disassociation & Recycling (+ microtubles/microfilaments/ATP/ MAP-2/kinesin/Rab3A/kinase/phosphatase) Transport aSNAP/ NSF ATP Ca2+ ATP Primed Fusion Pore Docked Plasma Membrane (VAMP2/Syntaxin/ SNAP-25/CAPS) (VAMP2/Syntaxin/SNAP-25/ synaptotagmin/syncollin) Pre-Docking (VAMP2/Syntaxin/ SNAP-25) (+ Rab3A/Rab27/RIM2/munc18/ piccolo/bassoon/Exos) READILY RELEASABLE POOL Schematic Representation of the Putative Steps in the Mechanism of Insulin Exocytosis & ß-Granule Trafficking in Pancreatic ß-cells Rhodes

  3. Golgi cargo aggregation Endosomal fusions Kiss & run retrieval Primary DCV sorting Secondary DCV sorting Crystallisation & exocytosis DCV fusion Constitutive-like release Membrane Traffic BDC -Hutton

  4. Furin (PACE, SPC1) 794 a.a. (pCys)2 D H S Signal Peptide PC2 (SPC2) Pro-segment 637 D H S Catalytic domain PC1/3 (SPC3) 753 D H S P-Domain PACE4 (SP4) Cysteine rich region 969 (pCys)5 D H S PC4 (SPC5) Amphipathic Helix 654 D H S PC5/6A (SPC6A) Transmembrane 915 D H S (pCys)5 PC6B (SPC6B) Cytoplasmic D H S 1887 (pCys)22 PC7 (SPC7, LPC, PC7, PC8) D H S 783 PC Family Members BDC -Hutton

  5. K R PC2 PC1 R R Proinsulin K K CPE R R R R R CPH R Split 65,66 proinsulin Split 32,33 proinsulin K PC1 R R PC2 R Des 31,32 proinsulin Des 64,65 proinsulin R CPE R Diarginyl insulin Insulin Proinsulin Processing BDC -Hutton

  6. 180aa Preproinsulin A|F1 KTRR|E33 KR|G66 110aa Ins B-chain Ins A-Chain C-peptide Preproglucagon Q|R1 KR|H33 KR|H72 RGRR|D111 RK160 KR|N64 R|H78 GRR|H125 Glicentin Glucagon Oxyntomodulin GLP-1 GLP-2 GLP-1 (7-37amide) Preprosomatostatin G|A25 Q|R89 116aa F|L34 RERK|A103 Antrin ? Somatostatin 28 SS-14 Prepro Pancreatic polypeptide E|P33 RPRYGKR|H69 95 aa Pancreatic polypeptide Islet Prohormones BDC -Hutton

  7. PC1 Insulin PC1 Glucagon Localization of PC1 with Islet Hormones BDC -Hutton

  8. PC2 Insulin PC2 Glucagon Localization of Islet PC2 with islet hormones BDC -Hutton

  9. Insulin CPE CPE Glucagon Localization of CPE with islet hormones BDC -Hutton

  10. Chromogranin A 457aa A|L19 KK|H97 AKR|E228 S|L260 GGK|S322 KR|l358 RR|G393 RR|G457 KR|E134 RKGESR|S272 KR|W342 AR|A380 VR|G413 Vasostatin I Pancreastatin WE14 Betagranin (Vasostatin II) KRWSRMDQLAKELTAEKR WSRMDQLAKELTAE MDQLAKELT WSRMDQLAKEL SRMDQLAKELT RWSRMDQLAKELTAE KRLE GEDDPDRSMKLSFRAR FRARAYGFRDPGPQLRRG AYGFRDPGPQL YGFRDPGPQL GFRDPGPQL FRDPGPQLR CgA products RRAEDQELESLSAIEAELEKVAHQLQALRR AEDQELESLSAIEAELEKVAHQLQAL ESLSAIEAELEKVAHQLQALRR BDC -Hutton

  11. Preproamylin PC1 PC2 A|T23 KR|K34 GKR|N74 89aa IAPP amide Proamylin Processing BDC -Hutton

  12. 7B2 Insulin Glucagon 7B2 Localization of 7B2 with islet hormones BDC -Hutton

  13. proSAAS Insulin proSAAS Glucagon Localization of proSAAS with islet hormones BDC -Hutton

  14. Extrapancreatic insulin-producing cells in multiple organs in diabetesKojima et al. PNAS 2004; 101:2458-2463 • Proinsulin mRNA and proinsulin protein induced with multiple forms of hyperglycemia in marrow derived CD45+ murine cells (in liver, adipose tissue, spleen, bone marrow and thymus[some acinar pancreas but not remnant islets]) STZ rat and mice; ob/ob mice/IP glucose X 3 days • Transgenic GFP driven by mouse insulin promoter gave complete concordance with presence proinsulin • Bone marrow transplantation experiments (bta galactosidase postive cells)indicated bone marrow derivation-Post glucose injections 30% of bone marrow cells positive for proinsulin and 75% of proinsulin positive cells beta galactosidase positive. • Proinsulin and somatostatin protein in same cells of liver of glucose injected mice. BDC

More Related