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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.

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

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  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

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