Differential pathway coupling of the activated insulin receptor drives signaling selectivity by XMetA, an allosteric partial agonist antibody

Journal of Pharmacology and Experimental Therapeutics

Volumn 353, Issue 1, 2015, Pages 35-43

  Bedinger, Daniel H ^a,c   Goldfine, Ira D ^a   Corbin, John A ^a   Roell, Marina K ^a   Adams, Sean H ^b,c  

^a XOMA Corporation   (United States)

^b Obesity and Metabolism Research Unit   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN; INSULIN RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY XMETA; PROTEIN KINASE B; THREONINE; TYROSINE; UNCLASSIFIED DRUG; ISOPROTEIN; PROTEIN BINDING;

ANIMAL CELL; BINDING AFFINITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG POTENCY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FEMALE; HUMAN; INCUBATION TIME; INSULIN BINDING; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR SENSITIVITY; REVIEW; SIGNAL TRANSDUCTION; AGONISTS; ALLOSTERISM; ANIMAL; CHO CELL LINE; CRICETULUS; IMMUNOLOGY; METABOLISM; PARTIAL AGONISM; PHOSPHORYLATION;

ALLOSTERIC REGULATION; ANIMALS; ANTIBODIES, MONOCLONAL; CHO CELLS; CRICETULUS; DRUG PARTIAL AGONISM; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HUMANS; INSULIN; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN ISOFORMS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION;

EID: 84923376166     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.114.221309     Document Type: Review

References (62)

1. Bhaskar V, Goldfine ID, Bedinger DH, Lau A, Kuan HF, Gross LM, Handa M, Maddux BA, Watson SR, Zhu S, et al. (2012) A fully human, allosteric monoclonal antibody that activates the insulin receptor and improves glycemic control. Diabetes 61:1263-1271.
2. Bhaskar V, Lau A, Goldfine ID, Narasimha AJ, Gross LM, Wong S, Cheung B, White ML, and Corbin JA (2013) XMetA, an allosteric monoclonal antibody to the insulin receptor, improves glycaemic control in mice with diet-induced obesity. Diabetes Obes Metab 15:272-275.
3. Ceresa BP, Kao AW, Santeler SR, and Pessin JE (1998) Inhibition of clathrinmediated endocytosis selectively attenuates specific insulin receptor signal transduction pathways. Mol Cell Biol 18:3862-3870.
4. Ceresa BP and Pessin JE (1998) Insulin regulation of the Ras activation/inactivation cycle. Mol Cell Biochem 182:23-29.
5. Currie CJ, Poole CD, and Gale EA (2009) The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 52:1766-1777.
6. Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, DeFronzo RA, Kahn CR, and Mandarino LJ (2000) Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 105:311-320.
7. Defronzo RA (2009) Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58:773-795.
8. De Meyts P (2008) The insulin receptor: a prototype for dimeric, allosteric membrane receptors? Trends Biochem Sci 33:376-384.
9. Dong XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, and White MF (2008) Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab 8:65-76.
10. Ellis L, Clauser E, Morgan DO, Edery M, Roth RA, and Rutter WJ (1986) Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell 45:721-732.
11. Fiory F, Alberobello AT, Miele C, Oriente F, Esposito I, Corbo V, Ruvo M, Tizzano B, Rasmussen TE, Gammeltoft S, et al. (2005) Tyrosine phosphorylation of phosphoinositidedependent kinase 1 by the insulin receptor is necessary for insulin metabolic signaling. Mol Cell Biol 25:10803-10814.
12. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, and Vigneri R (1999) Insulin receptor isoform A, a newly recognized, highaffinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol 19:3278-3288.
13. Garg SK, Hirsch IB, and Skyler JS (2009) Insulin glargine and cancer-an unsubstantiated allegation. Diabetes Technol Ther 11:473-476.
14. Glendorf T, Stidsen CE, Norrman M, Nishimura E, Sørensen AR, and Kjeldsen T (2011) Engineering of insulin receptor isoform-selective insulin analogues. PLoS ONE 6:e20288.
15. Grouven U, Hemkens LG, Bender R, and Sawicki PT (2010) Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues. Reply to Nagel JM, Mansmann U, Wegscheider K, et al. [letter] and Simon D [letter]. (Letter) Diabetologia 53:209-211.
16. Hansen BF, Danielsen GM, Drejer K, Sørensen AR, Wiberg FC, Klein HH, and Lundemose AG (1996) Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency. Biochem J 315:271-279.
17. Hansen BF, Kurtzhals P, Jensen AB, Dejgaard A, and Russell-Jones D (2011) Insulin X10 revisited: a super-mitogenic insulin analogue. Diabetologia 54:2226-2231.
18. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke GW, and Sawicki PT (2009) Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia 52:1732-1744.
19. Hilgenfeld R, Seipke G, Berchtold H, and Owens DR (2014) The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs 74:911-927.
20. Hubbard SR (2013) The insulin receptor: both a prototypical and atypical receptor tyrosine kinase. Cold Spring Harb Perspect Biol 5:a008946.
21. Ish-Shalom D, Christoffersen CT, Vorwerk P, Sacerdoti-Sierra N, Shymko RM, Naor D, and De Meyts P (1997) Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetologia 40(Suppl 2):S25-S31.
22. Issafras H, Bedinger DH, Corbin JA, Goldfine ID, Bhaskar V, White ML, Rubin P, and Scannon PJ (2014) Selective allosteric antibodies to the insulin receptor for the treatment of hyperglycemic and hypoglycemic disorders. J Diabetes Sci Technol 8:865-873.
23. Janssen JA and Varewijck AJ (2014) Insulin analogs and cancer: a note of caution. Front Endocrinol (Lausanne) 5:79.
24. Jensen M, Hansen B, De Meyts P, Schäffer L, and Ursø B (2007) Activation of the insulin receptor by insulin and a synthetic peptide leads to divergent metabolic and mitogenic signaling and responses. J Biol Chem 282:35179-35186.
25. Jiang ZY, Lin YW, Clemont A, Feener EP, Hein KD, Igarashi M, Yamauchi T, White MF, and King GL (1999) Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J Clin Invest 104:447-457.
26. Johnson GL and Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911-1912.
27. Johnson JA and Yasui Y (2010) Glucose-lowering therapies and cancer risk: the trials and tribulations of trials and observations. Diabetologia 53:1823-1826.
28. Kahn CR (1978) Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 27(Suppl 2):1893-1902.
29. Kahn CR (1985) The molecular mechanism of insulin action. Annu Rev Med 36:429-451.
30. Kenakin T, Watson C, Muniz-Medina V, Christopoulos A, and Novick S (2012) A simple method for quantifying functional selectivity and agonist bias. ACS Chem Neurosci 3:193-203.
31. Knudsen L, De Meyts P, and Kiselyov VV (2011) Insight into the molecular basis for the kinetic differences between the two insulin receptor isoforms. Biochem J 440:397-403.
32. Kurtzhals P, Schäffer L, Sørensen A, Kristensen C, Jonassen I, Schmid C, and Trüb T (2000) Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 49:999-1005.
33. Maegawa H, McClain DA, Freidenberg G, Olefsky JM, Napier M, Lipari T, Dull TJ, Lee J, and Ullrich A (1988) Properties of a human insulin receptor with a COOH-terminal truncation. II. Truncated receptors have normal kinase activity but are defective in signaling metabolic effects. J Biol Chem 263:8912-8917.
34. Malaguarnera R, Sacco A, Voci C, Pandini G, Vigneri R, and Belfiore A (2012) Proinsulin binds with high affinity the insulin receptor isoform A and predominantly activates the mitogenic pathway. Endocrinology 153:2152-2163.
35. McClain DA, Maegawa H, Levy J, Huecksteadt T, Dull TJ, Lee J, Ullrich A, and Olefsky JM (1988) Properties of a human insulin receptor with a COOH-terminal truncation. I. Insulin binding, autophosphorylation, and endocytosis. J Biol Chem 263:8904-8911.
36. Mîinea CP, Sano H, Kane S, Sano E, Fukuda M, Peränen J, Lane WS, and Lienhard GE (2005) AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J 391:87-93.
37. Moller DE, Yokota A, Caro JF, and Flier JS (1989) Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol Endocrinol 3:1263-1269.
38. Morcavallo A, Genua M, Palummo A, Kletvikova E, Jiracek J, Brzozowski AM, Iozzo RV, Belfiore A, and Morrione A (2012) Insulin and insulin-like growth factor II differentially regulate endocytic sorting and stability of insulin receptor isoform A. J Biol Chem 287:11422-11436.
39. Mosthaf L, Grako K, Dull TJ, Coussens L, Ullrich A, and McClain DA (1990) Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J 9:2409-2413.
40. Nagel JM, Mansmann U, Wegscheider K, and Röhmel J (2010) Insulin resistance and increased risk for malignant neoplasms: confounding of the data on insulin glargine. Diabetologia 53:206-208.
41. Nicolucci A (2010) Epidemiological aspects of neoplasms in diabetes. Acta Diabetol 47:87-95.
42. Pollock RF, Erny-Albrecht KM, Kalsekar A, Bruhn D, and Valentine WJ (2011) Longacting insulin analogs: a review of "real-world" effectiveness in patients with type 2 diabetes. Curr Diabetes Rev 7:61-74.
43. Rathanaswami P, Babcook J, and Gallo M (2008) High-affinity binding measurements of antibodies to cell-surface-expressed antigens. Anal Biochem 373:52-60.
44. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595-1607.
45. Roth RA and Cassell DJ (1983) Insulin receptor: evidence that it is a protein kinase. Science 219:299-301.
46. Schwimmer LJ, Huang B, Giang H, Cotter RL, Chemla-Vogel DS, Dy FV, Tam EM, Zhang F, Toy P, Bohmann DJ, et al. (2013) Discovery of diverse and functional antibodies from large human repertoire antibody libraries. J Immunol Methods 391:60-71.
47. Sciacca L, Cassarino MF, Genua M, Pandini G, Le Moli R, Squatrito S, and Vigneri R (2010) Insulin analogues differently activate insulin receptor isoforms and postreceptor signalling. Diabetologia 53:1743-1753.
48. Sesti G, Tullio AN, D'Alfonso R, Napolitano ML, Marini MA, Borboni P, Longhi R, Albonici L, Fusco A, Aglianò AM, et al. (1994) Tissue-specific expression of two alternatively spliced isoforms of the human insulin receptor protein. Acta Diabetol 31:59-65.
49. Shia MA and Pilch PF (1983) The beta subunit of the insulin receptor is an insulinactivated protein kinase. Biochemistry 22:717-721.
50. Takata Y, Webster NJ, and Olefsky JM (1991) Mutation of the two carboxyl-terminal tyrosines results in an insulin receptor with normal metabolic signaling but enhanced mitogenic signaling properties. J Biol Chem 266:9135-9139.
51. Tan SX, Ng Y, Meoli CC, Kumar A, Khoo PS, Fazakerley DJ, Junutula JR, Vali S, James DE, and Stöckli J (2012) Amplification and demultiplexing in insulinregulated Akt protein kinase pathway in adipocytes. J Biol Chem 287:6128-6138.
52. Taniguchi CM, Emanuelli B, and Kahn CR (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7:85-96.
53. Ussar S, Vienberg SG, and Kahn CR (2011) Receptor antibodies as novel therapeutics for diabetes. Sci Transl Med 3:113ps147.
54. Vigneri P, Frasca F, Sciacca L, Pandini G, and Vigneri R (2009) Diabetes and cancer. Endocr Relat Cancer 16:1103-1123.
55. Vigneri R, Squatrito S, and Frittitta L (2012) Selective insulin receptor modulators (SIRM): a new class of antidiabetes drugs? Diabetes 61:984-985.
56. White MF, Livingston JN, Backer JM, Lauris V, Dull TJ, Ullrich A, and Kahn CR (1988) Mutation of the insulin receptor at tyrosine 960 inhibits signal transmission but does not affect its tyrosine kinase activity. Cell 54:641-649.
57. Whitten AE, Smith BJ, Menting JG, Margetts MB, McKern NM, Lovrecz GO, Adams TE, Richards K, Bentley JD, Trewhella J, et al. (2009) Solution structure of ectodomains of the insulin receptor family: the ectodomain of the type 1 insulin-like growth factor receptor displays asymmetry of ligand binding accompanied by limited conformational change. J Mol Biol 394:878-892.
58. Wilden PA, Backer JM, Kahn CR, Cahill DA, Schroeder GJ, and White MF (1990) The insulin receptor with phenylalanine replacing tyrosine-1146 provides evidence for separate signals regulating cellular metabolism and growth. Proc Natl Acad Sci USA 87:3358-3362.
59. Xie L, Mark Jones R, Glass TR, Navoa R, Wang Y, and Grace MJ (2005) Measurement of the functional affinity constant of a monoclonal antibody for cell surface receptors using kinetic exclusion fluorescence immunoassay. J Immunol Methods 304:1-14.
60. Yamaguchi Y, Flier JS, Benecke H, Ransil BJ, and Moller DE (1993) Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology 132:1132-1138.
61. Yamaguchi Y, Flier JS, Yokota A, Benecke H, Backer JM, and Moller DE (1991) Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology 129:2058-2066.
62. Zhao J, Linden E, der K, Cao L, Shimizu R, Hansen BC, Rubin P, and Bezwada P (2014) XMetA, a novel insulin receptor activator, is efficacious in glycemic control in rhesus monkeys with naturally-occurring type 2 diabetes, in Proceedings of the American Diabetes Association 74th Scientific Sessions; 2014 June 13-17; San Francisco, CA. Vol. 63 (Suppl 1) Abstract 123-OR, American Diabetes Association, Alexandria, VA.