Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin

Best Practice and Research: Clinical Endocrinology and Metabolism

Volumn 28, Issue 1, 2014, Pages 3-13

  Cheng, Kenneth K Y ^a   Lam, Karen S L ^a   Wang, Baile ^a   Xu, Aimin ^a  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

adiponectin; APPL1; diabetes; insulin; obesity

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ADAPTOR PROTEIN; ADAPTOR PROTEIN APPL1; ADIPONECTIN; ADIPONECTIN RECEPTOR 1; ADIPONECTIN RECEPTOR 2; GLUCOSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; INSULIN RECEPTOR SUBSTRATE; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; RECOMBINANT ADIPONECTIN; RECOMBINANT PROTEIN; SNARE PROTEIN; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ANTIDIABETIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; CELL PROLIFERATION; CONFERENCE PAPER; ENZYME ACTIVATION; FATTY ACID OXIDATION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TRANSPORT; HUMAN; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIUM;

ADIPONECTIN; APPL1; DIABETES; INSULIN; OBESITY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADIPONECTIN; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; HUMANS; INSULIN; INSULIN RESISTANCE; OBESITY; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTORS, ADIPONECTIN; SIGNAL TRANSDUCTION;

EID: 85047689168     PISSN: 1521690X     EISSN: 15321908     Source Type: Journal    
DOI: 10.1016/j.beem.2013.06.006     Document Type: Conference Paper

References (82)

1. C. Rask-Madsen, and C.R. Kahn Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease Arteriosclerosis, Thrombosis, and Vascular Biology 32 9 2012 2052 2059
2. E. Maury, and S.M. Brichard Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome Molecular and Cellular Endocrinology 314 1 2010 1 16
3. W. Zhu, K.K. Cheng, P.M. Vanhoutte, K.S. Lam, and A. Xu Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention Clinical Science 114 5 2008 361 374
4. V.T. Samuel, and G.I. Shulman Mechanisms for insulin resistance: common threads and missing links Cell 148 5 2012 852 871
5. A.C. Konner, and J.C. Bruning Selective insulin and leptin resistance in metabolic disorders Cell Metabolism 16 2 2012 144 152
6. A.S. Lihn, T. Ostergard, B. Nyholm, S.B. Pedersen, B. Richelsen, and O. Schmitz Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients American Journal of Physiology. Endocrinology and Metabolism 284 2 2003 E443 E448
7. T. Yamauchi, and T. Kadowaki Adiponectin receptor as a key player in healthy longevity and obesity-related diseases Cell Metabolism 17 2 2013 185 196
8. H. Gao, T. Fall, R.M. van Dam, A. Flyvbjerg, B. Zethelius, and E. Ingelsson et al. Evidence of a Causal Relationship Between Adiponectin Levels and Insulin Sensitivity: A Mendelian Randomization Study Diabetes 62 4 2013 1338 1344
9. T. Yamauchi, J. Kamon, H. Waki, Y. Terauchi, N. Kubota, and K. Hara et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity Nature Medicine 7 8 2001 941 946
10. A.H. Berg, T.P. Combs, X. Du, M. Brownlee, and P.E. Scherer The adipocyte-secreted protein Acrp30 enhances hepatic insulin action Nature Medicine 7 8 2001 947 953
11. J. Fruebis, T.S. Tsao, S. Javorschi, D. Ebbets-Reed, M.R. Erickson, and F.T. Yen et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice Proceedings of the National Academy of Sciences of the United States of America 98 4 2001 2005 2010
12. T. Yamauchi, J. Kamon, H. Waki, Y. Imai, N. Shimozawa, and K. Hioki et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis Journal of Biological Chemistry 278 4 2003 2461 2468
13. N. Kubota, Y. Terauchi, T. Yamauchi, T. Kubota, M. Moroi, and J. Matsui et al. Disruption of adiponectin causes insulin resistance and neointimal formation Journal of Biological Chemistry 277 29 2002 25863 25866
14. N. Maeda, I. Shimomura, K. Kishida, H. Nishizawa, M. Matsuda, and H. Nagaretani et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 Nature Medicine 8 7 2002 731 737
15. A.R. Nawrocki, M.W. Rajala, E. Tomas, U.B. Pajvani, A.K. Saha, and M.E. Trumbauer et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists Journal of Biological Chemistry 281 5 2006 2654 2660
16. R.A. Miller, Q. Chu, J. Le Lay, P.E. Scherer, R.S. Ahima, and K.H. Kaestner et al. Adiponectin suppresses gluconeogenic gene expression in mouse hepatocytes independent of LKB1-AMPK signaling Journal of Clinical Investigation 121 6 2011 2518 2528
17. M. Awazawa, K. Ueki, K. Inabe, T. Yamauchi, N. Kubota, and K. Kaneko et al. Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway Cell Metabolism 13 4 2011 401 412
18. R.B. Ceddia, R. Somwar, A. Maida, X. Fang, G. Bikopoulos, and G. Sweeney Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells Diabetologia 48 1 2005 132 139
19. T. Yamauchi, J. Kamon, Y. Minokoshi, Y. Ito, H. Waki, and S. Uchida et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase Nature Medicine 8 11 2002 1288 1295
20. A. Xu, Y. Wang, H. Keshaw, L.Y. Xu, K.S. Lam, and G.J. Cooper The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice Journal of Clinical Investigation 112 1 2003 91 100
21. Y. Wang, G. Lu, W.P. Wong, J.F. Vliegenthart, G.J. Gerwig, and K.S. Lam et al. Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum Proteomics 4 12 2004 3933 3942
22. M. Iwabu, T. Yamauchi, M. Okada-Iwabu, K. Sato, T. Nakagawa, and M. Funata et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1 Nature 464 7293 2010 1313 1319
23. T. Kubota, N. Kubota, H. Kumagai, S. Yamaguchi, H. Kozono, and T. Takahashi et al. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle Cell Metabolsim 13 3 2011 294 307
24. H. Chen, M. Montagnani, T. Funahashi, I. Shimomura, and M.J. Quon Adiponectin stimulates production of nitric oxide in vascular endothelial cells Journal of Biological Chemistry 278 45 2003 45021 45026
25. W.L. Holland, R.A. Miller, Z.V. Wang, K. Sun, B.M. Barth, and H.H. Bui et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin Nature Medicine 17 1 2011 55 63
26. N. Wijesekara, M. Krishnamurthy, A. Bhattacharjee, A. Suhail, G. Sweeney, and M.B. Wheeler Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion Journal of Biological Chemistry 285 44 2010 33623 33631
27. D. Dietze-Schroeder, H. Sell, M. Uhlig, M. Koenen, and J. Eckel Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors Diabetes 54 7 2005 2003 2011
28. J.Y. Kim, E. van de Wall, M. Laplante, A. Azzara, M.E. Trujillo, and S.M. Hofmann et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue Journal of Clinical Investigation 117 9 2007 2621 2637
29. T. Yokota, K. Oritani, I. Takahashi, J. Ishikawa, A. Matsuyama, and N. Ouchi et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages Blood 96 5 2000 1723 1732
30. K.M. Ajuwon, and M.E. Spurlock Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 288 5 2005 R1220 R1225
31. M. Kumada, S. Kihara, N. Ouchi, H. Kobayashi, Y. Okamoto, and K. Ohashi et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages Circulation 109 17 2004 2046 2049
32. V. Zacharioudaki, A. Androulidaki, A. Arranz, G. Vrentzos, A.N. Margioris, and C. Tsatsanis Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression Journal of Immunology 182 10 2009 6444 6451
33. T. Yamauchi, J. Kamon, Y. Ito, A. Tsuchida, T. Yokomizo, and S. Kita et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects Nature 423 6941 2003 762 769
34. T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, and K. Tobe Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome Journal of Clinical Investigation 116 7 2006 1784 1792
35. T. Yamauchi, Y. Nio, T. Maki, M. Kobayashi, T. Takazawa, and M. Iwabu et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions Nature Medicine 13 3 2007 332 339
36. G.J. King, J. Stockli, S.H. Hu, B. Winnen, W.G. Duprez, and C.C. Meoli et al. Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase Journal of Biological Chemistry 287 49 2012 40996 41006
37. S.H. Um, F. Frigerio, M. Watanabe, F. Picard, M. Joaquin, and M. Sticker et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity Nature 431 7005 2004 200 205
38. C. Wang, X. Mao, L. Wang, M. Liu, M.D. Wetzel, and K.L. Guan et al. Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1 Journal of Biological Chemistry 282 11 2007 7991 7996
39. S.S. Deepa, and L.Q. Dong APPL1: role in adiponectin signaling and beyond. American Journal of Physiology Endocrinology and Metabolism 296 1 2009 E22 E36
40. Y. Mitsuuchi, S.W. Johnson, G. Sonoda, S. Tanno, E.A. Golemis, and J.R. Testa Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2 Oncogene 18 35 1999 4891 4898
41. M. Miaczynska, S. Christoforidis, A. Giner, A. Shevchenko, S. Uttenweiler-Joseph, and B. Habermann et al. APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment Cell 116 3 2004 445 456
42. K.K. Cheng, M.A. Iglesias, K.S. Lam, Y. Wang, G. Sweeney, and W. Zhu et al. APPL1 potentiates insulin-mediated inhibition of hepatic glucose production and alleviates diabetes via Akt activation in mice Cell Metabolism 9 5 2009 417 427
43. T. Saito, C.C. Jones, S. Huang, M.P. Czech, and P.F. Pilch The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation Journal of Biological Chemistry 282 44 2007 32280 32287
44. I. Pilecka, L. Sadowski, Y. Kalaidzidis, and M. Miaczynska Recruitment of APPL1 to ubiquitin-rich aggresomes in response to proteasomal impairment Experimental Cell Research 317 8 2011 1093 1107
45. J.A. Broussard, W.H. Lin, D. Majumdar, B. Anderson, B. Eason, and C.M. Brown et al. The endosomal adaptor protein APPL1 impairs the turnover of leading edge adhesions to regulate cell migration Molecular Biology of the Cell 23 8 2012 1486 1499
46. R. Zoncu, R.M. Perera, D.M. Balkin, M. Pirruccello, D. Toomre, and P. De Camilli A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes Cell 136 6 2009 1110 1121
47. A. Schenck, L. Goto-Silva, C. Collinet, M. Rhinn, A. Giner, and B. Habermann et al. The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development Cell 133 3 2008 486 497
48. A. Hupalowska, B. Pyrzynska, and M. Miaczynska APPL1 regulates basal NF-kappaB activity by stabilizing NIK Journal of Cell Science 125 Pt 17 2012 4090 4102
49. G. Zhu, J. Chen, J. Liu, J.S. Brunzelle, B. Huang, and N. Wakeham et al. Structure of the APPL1 BAR-PH domain and characterization of its interaction with Rab5 EMBO Journal 26 14 2007 3484 3493
50. J. Li, X. Mao, L.Q. Dong, F. Liu, and L. Tong Crystal structures of the BAR-PH and PTB domains of human APPL1 Structure 15 5 2007 525 533
51. R.L. Gant-Branum, J.A. Broussard, A. Mahsut, D.J. Webb, and J.A. McLean Identification of phosphorylation sites within the signaling adaptor APPL1 by mass spectrometry Journal of Proteome Research 9 3 2010 1541 1548
52. M. Liu, L. Zhou, L. Wei, R. Villarreal, X. Yang, and D. Hu et al. Phosphorylation of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif 1 (APPL1) at Ser430 mediates endoplasmic reticulum (ER) stress-induced insulin resistance in hepatocytes Journal of Biological Chemistry 287 31 2012 26087 26093
53. R. Marinho, E.R. Ropelle, D.E. Cintra, C.T. De Souza, A.S. Da Silva, and F.C. Bertoli et al. Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss Journal of Cellular Physiology 227 7 2012 2917 2926
54. K.K. Cheng, K.S. Lam, D. Wu, Y. Wang, G. Sweeney, and R.L. Hoo et al. APPL1 potentiates insulin secretion in pancreatic beta cells by enhancing protein kinase Akt-dependent expression of SNARE proteins in mice Proceedings of the National Academy of Sciences of the United States of America 109 23 2012 8919 8924
55. K.K. Cheng, K.S. Lam, Y. Wang, Y. Huang, D. Carling, and D. Wu et al. Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells Diabetes 56 5 2007 1387 1394
56. P.M. Schmid, M. Resch, A. Steege, S. Fredersdorf-Hahn, B. Stoelcker, and C. Birner et al. Globular and full-length adiponectin induce NO-dependent vasodilation in resistance arteries of Zucker lean but not Zucker diabetic fatty rats American Journal of Hypertension 24 3 2011 270 277
57. S.A. Patel, K.L. Hoehn, R.T. Lawrence, L. Sawbridge, N.A. Talbot, and J.L. Tomsig et al. Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity Endocrinology 153 11 2012 5231 5246
58. R.M. Holmes, Z. Yi, E. De Filippis, R. Berria, S. Shahani, and P. Sathyanarayana et al. Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling Diabetologia 54 8 2011 2122 2131
59. Y. Xu, N. Wang, F. Ling, P. Li, and Y. Gao Receptor for activated C-kinase 1, a novel binding partner of adiponectin receptor 1 Biochemical and Biophysical Research Communications 378 1 2009 95 98
60. J.T. Heiker, C.M. Wottawah, C. Juhl, D. Kosel, K. Morl, and A.G. Beck-Sickinger Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling Cellular Signalling 21 6 2009 936 942
61. H.K. Charlton, J. Webster, S. Kruger, F. Simpson, A.A. Richards, and J.P. Whitehead ERp46 binds to AdipoR1, but not AdipoR2, and modulates adiponectin signalling Biochemical and Biophysical Research Communications 392 2 2010 234 239
62. X. Mao, C.K. Kikani, R.A. Riojas, P. Langlais, L. Wang, and F.J. Ramos et al. APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function Nature Cell Biology 8 5 2006 516 523
63. A. Coope, M. Milanski, E.P. Araujo, M. Tambascia, M.J. Saad, and B. Geloneze et al. AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus FEBS Letters 582 10 2008 1471 1476
64. B. Chandrasekar, W.H. Boylston, K. Venkatachalam, N.J. Webster, S.D. Prabhu, and A.J. Valente Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMP-activated protein kinase (AMPK) activation and IKK/NF-kappaB/PTEN suppression Journal of Biological Chemistry 283 36 2008 24889 24898
65. K.H. Chan, K.S. Lam, O.Y. Cheng, J.S. Kwan, P.W. Ho, and K.K. Cheng et al. Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity PLoS ONE 7 12 2012 e52354
66. L. Tian, N. Luo, X. Zhu, B.H. Chung, W.T. Garvey, and Y. Fu Adiponectin-AdipoR1/2-APPL1 signaling axis suppresses human foam cell formation: differential ability of AdipoR1 and AdipoR2 to regulate inflammatory cytokine responses Atherosclerosis 221 1 2012 66 75
67. X. Fang, R. Palanivel, J. Cresser, K. Schram, R. Ganguly, and F.S. Thong et al. An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart. American Journal of Physiology Endocrinology and Metabolism 299 5 2010 E721 E729
68. M.H. Lee, R.L. Klein, H.M. El-Shewy, D.K. Luttrell, and L.M. Luttrell The adiponectin receptors AdipoR1 and AdipoR2 activate ERK1/2 through a Src/Ras-dependent pathway and stimulate cell growth Biochemistry 47 44 2008 11682 11692
69. D. Fan, L. Li, C. Wang, X.B. Cui, Y. Zhou, and L.L. Wu Adiponectin induces interleukin-6 production and its underlying mechanism in adult rat cardiac fibroblasts Journal of Cellular Physiology 226 7 2011 1793 1802
70. L. Zhou, S.S. Deepa, J.C. Etzler, J. Ryu, X. Mao, and Q. Fang et al. Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways Journal of Biological Chemistry 284 33 2009 22426 22435
71. S.S. Deepa, L. Zhou, J. Ryu, C. Wang, X. Mao, and C. Li et al. APPL1 mediates adiponectin-induced LKB1 cytosolic localization through the PP2A-PKCzeta signaling pathway Molecular Endocrinology 25 10 2011 1773 1785
72. X. Fang, J. Fetros, K.E. Dadson, A. Xu, and G. Sweeney Leptin prevents the metabolic effects of adiponectin in L6 myotubes Diabetologia 52 10 2009 2190 2200
73. X. Xin, L. Zhou, C.M. Reyes, F. Liu, and L.Q. Dong APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway. American Journal of Physiology Endocrinology and Metabolism 300 1 2011 E103 E110
74. H.J. Chial, P. Lenart, and Y.Q. Chen APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy PLoS ONE 5 8 2010 e12471
75. H.J. Chial, R. Wu, C.V. Ustach, L.C. McPhail, W.C. Mobley, and Y.Q. Chen Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides Traffic 9 2 2008 215 229
76. C. Wang, X. Xin, R. Xiang, F.J. Ramos, M. Liu, and H.J. Lee et al. Yin-Yang regulation of adiponectin signaling by APPL isoforms in muscle cells Journal of Biological Chemistry 284 46 2009 31608 31615
77. M.E. Cleasby, Q. Lau, E. Polkinghorne, S.A. Patel, S.J. Leslie, and N. Turner et al. The adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway Journal of Endocrinology 210 1 2011 81 92
78. K. Du, S. Herzig, R.N. Kulkarni, and M. Montminy TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver Science 300 5625 2003 1574 1577
79. Y. Wang, K.K. Cheng, K.S. Lam, D. Wu, Y. Huang, and P.M. Vanhoutte et al. APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice Diabetes 60 11 2011 3044 3054
80. I.B. Leibiger, B. Leibiger, and P.O. Berggren Insulin signaling in the pancreatic beta-cell Annual Review of Nutrition 28 2008 233 251
81. K. Kaneko, K. Ueki, N. Takahashi, S. Hashimoto, M. Okamoto, and M. Awazawa et al. Class IA phosphatidylinositol 3-kinase in pancreatic beta cells controls insulin secretion by multiple mechanisms Cell Metabolism 12 6 2010 619 632
82. J.L. Jewell, E. Oh, and D.C. Thurmond Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4. American Journal of Physiology. Regulatory Integrative and Comparative Physiology 298 3 2010 R517 R531