Julio-Septiembre 2017 71
ISSN 1317-987X


Insulina. Estructura, síntesis, secreción, depuración y degradación (Revisión)


1. Bliss M. 1982. The Discovery of Insulin. Chicago: University of Chicago Press 6.

2. Leslie RGD and Robbins DC 1995 Diabetes: Clinical Science in Practice, Cambridge University Press 221-271.

3. Von Mering J and Minkowski O 1890 Diabetes mellitus nach pankreas exterpation. Arch Exp Path Pharmacol (Leipzig) 26:371.

4. Schafer EA 1916. An introduction to the study of internal secretion. In: The Endocrine Organs. London: Longmans, Gree.

5. Barron M. 1920. The relation of the islets of Langerhans to diabetes with special referenceto cases of pancreatic lithiasis. Surg Gynecol Obstet 31:437-448.

6. Banting FG and Best CH. 1921. The internal secretion of the pancreas. J Lab Clin Med 7:247-253

7. Abel JJ. 1926. Crystalline insulin. Proc Natl Acad Sci. 12: 132–136.

8. Sanger F. 1959. Chemistry of insulin; determination of the structure of insulin opens the way to greater understanding of life processes. Science. 129: 1340-1344

9. Fu Z. Gilbert ER. and Liu D. 2013. Regulation of Insulin Synthesis and Secretion and Pancreatic Beta-Cell Dysfunction in Diabetes. Curr Diabetes Rev. 9: 25–53.

10. Baker EN, Blundell TL, Cutfield JF, Cutfield SM, Dodson EJ, Dodson GG, Hodgkin DC, Hubbard RE, Isaacs NW, Reynolds CD, Sakabe K, Sakabe N, Vijayan M. 1988. The structure of 2 Zn pig insulin crystals at 1.5 A resolution. Philos Trans R Soc London. B319:369–456.

11. De Meyts P. 2004.Insulin and its receptor: structure, function and evolution. Bioessays. 26: 1351–62.

12. Chan SJ, Keim P, and Steiner DF. 1976. Cell-free synthesis of rat preproinsulins: characterization and partial amino acid sequence determination. Proc. Natl. Acad. Sci. U. S. A. 73: 1964-1968.

13. Harper ME. Ullrich A. and Saunders GF. 1981. Localization of the human insulin gene to the distal end of the short arm of chromosome 11. Proc. Nat. Acad. Sci. 78: 4458-4460,

14. Bell, G.I., Pictet, R.L., Rutter, W.J., Cordell, B., Tischer, E., and Goodman, H.M. 1980. Sequence of the human insulin gene. Nature 284:26-32.

15. Egea PF, Stroud RM and Walter P. 2005.Targeting proteins to membranes: structure of the signal recognition particle. Curr Opin Struct Biol. 15: 213–20.

16. Lomedico PT, Chan SJ, Steiner DF and Saunders GF. 1977. Immunological and chemical characterization of bovine preproinsulin. J Biol Chem. 252: 7971–7978.

17. Patzelt C, Labrecque AD, Duguid JR, Carroll RJ, Keim PS, Heinrikson RL, and Steiner DF. 1978. Detection and kinetic behavior of preproinsulin in pancreatic islets. Proc Natl Acad Sci U S A. 75: 1260–1264.

18. Huang XF and Arvan P. 1995. Intracellular transport of proinsulin in pancreatic beta-cells. Structural maturation probed by disulfide accessibility. J Biol Chem. 270: 20417–20423.

19. Munro S and Pelham HR. 1987. A C-terminal signal prevents secretion of luminal ER proteins. Cell. 48: 899–907.

20. Smeekens SP, Albiges-Rizo C, Carroll R, Martin S, Ohagi S, Phillips LA, Benig M, Gardner P, Montag AG, Swift HH, Thomas G and Steiner DF 1992 Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3. Proc Natl Acad Sci USA 89:8822-8826.

21. Davidson HW, Wenzlau JM and O’Brien RM. 2014. Zinc transporter 8 (ZnT8) and beta cell function. Trends Endocrinol Metab. 25: 415–424.

22. Kwok SC, Steiner DF, Rubenstein AH amd Tager HS. 1983. Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago). Diabetes. 32: 872-875.

23. Nishi M and Nanjo K. 2011. Insulin gene mutations and diabetes. J Diabetes Investig. 2: 92–100.

24. Bucchini D, Ripoche MA, Stinnakre MG, Desbois P, Lores P, Monthioux E, Absil J, Lepesant JA, Pictet R and Jami J. 1986. Pancreatic expression of human insulin gene in transgenic mice. Proc Natl Acad Sci U S A. 83: 2511–2515.

25. Howell SL. 1984.The mechanism of insulin secretion. Diabetologia. 26: 319–327.

26. Hay CW and Docherty K. 2006. Comparative analysis of insulin gene promoters: implications for diabetes research. Diabetes. 55: 3201–3213.

27. Matsuoka TA, Artner I, Henderson E, Means A, Sander M and Stein R. 2004. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc Natl Acad Sci U S A. 101: 2930–2933.

28. Vander Mierde D, Scheuner D, Quintens R, Patel R, Song B, Tsukamoto K, Beullens M, Kaufman RJ, Bollen M and Schuit FC. 2007. Glucose activates a protein phosphatase-1-mediated signaling pathway to enhance overall translation in pancreatic beta-cells. Endocrinology. 148: 609–617.

29. Mziaut H, Trajkovski M, Kersting S, Ehninger A, Altkruger A, Lemaitre RP, Schmidt D, Saeger HD, Lee MS, Drechsel DN, Muller S and Solimena M. 2006. Synergy of glucose and growth hormone signalling in islet cells through ICA512 and STAT5. Nat Cell Biol. 8: 435–445.

30. Itoh N and Okamoto H. 1980.Translational control of proinsulin synthesis by glucose. Nature. 283: 100–102.

31. Giddings SJ, Chirgwin J and Permutt MA. 1982. Effects of glucose on proinsulin messenger RNA in rats in vivo. Diabetes. 31: 624–629.

32. Wicksteed B, Uchizono Y, Alarcon C, McCuaig JF, Shalev A and Rhodes CJ. 2007. A cis-element in the 5′ untranslated region of the preproinsulin mRNA (ppIGE) is required for glucose regulation of proinsulin translation. Cell Metab. 5: 221–227.

33. Schmitz O, Rungby J, Edge L and Juhl CB. 2008. On high-frequency insulin oscillations. Ageing Res Rev.7: 301–305.

34. Suckale J and Solimena M. 2008. Pancreas islets in metabolic signaling--focus on the beta-cell. Front Biosci.13: 7156–7171.

35. Nolan CJ and Prentki M. 2008. The islet beta-cell: fuel responsiveand vulnerable. Trends Endocrinol Metab 19: 285-291.

36. Nolan CJ, Madiraju MS, Delghnngaro-Augusto V, Peyot ML, and Prentiki M. 2006.Fatty acid signaling in the beta-cell and insulin secretion. Diabetes; 55 (Suppl 2): S16-23.

37. Ruiz De Azua I, Gautam D, Guettier JM and Wess J. 2011. Novel insights into the function of beta-cell M3 muscarinic acetylcholine receptors: Therapeutic implications. Trends Endocrinol Metab; 22: 74-80.

38. Ashcroft FM and Rorsman P. 2012. Diabetes mellitus and the beta cell: The last ten years. Cell 148: 1160-1171.

39. Zou C-Y, Gong Y and Liang, J. 2014. Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes. Eur. Rev. Med. Pharmacol. Sci. 18: 2215-2227.

40. Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, Girotti M, Marie S, Macdonald MJ, Wollheim CB and Rutter GA. 1994. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem. 269: 4895-4902.

41. Kwan EP and Gaisano HY. 2009. Rescuing the subprime meltdown in insulin exocytosis in diabetes. Ann N Y Acad Sci. 1152: 154-164.

42. Nolan CJ, Damm P and Prentki M. 2011. Type 2 diabetes across generations: From pathophysiology to prevention and management. Lancet. 378: 169-181.

43. Wang Z and Thurmond DC. 2009. Mechanisms of biphasic insulin-granule exocytosis—roles of the cytoskeleton, small GTPases and SNARE proteins. J Cell Sci. 122: 893-903.

44. Drucker DJ. 2006. The biology of incretin hormones. Cell Metab; 3: 153-165.

45. Ishii H, Sato Y, Takei M, Nishio S and Komatsu M. 2011. Glucose-incretin interaction revisited. Endocrine J. 58: 519-525.

46. Seino S, Takahashi H, Fujimoto W and Shibasaki T. 2009. Roles of cAMP signalling in insulin granule exocytosis. Diabetes Obes Metab 11: 180-188.

47. Seino S and Shibasaki T. 2005. "PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis". Physiol Rev. 85: 1303–1342.

48. Chang TW and Goldberg AL. 1978. The metabolic fates of amino acids and the formation of glutamine in skeletal muscle. J Biol Chem. 253: 3685–3693.

49. Nauck MA, Bartels E, Orskov C, Ebert R and Creutzfeldt W. 1993. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7–36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. JClin Endocrinol Metab. 76 : 912–917.

50. Dixon G, Nolan J, McClenaghan N, Flatt PR and Newsholme P. 2003. A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine. J Endocrinol.179: 447–454.

51. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, Ogi K, Hosoya M, Tanaka Y, Uejima H, Tanaka H, Maruyama M, Satoh R, Okubo S, Kizawa H, Komatsu H, Matsumura F, Noguchi Y, Shinohara T, Hinuma S, Fujisawa Y and Fujino M. 2003. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 422: 173–176.

52. Nadal A, Rovira JM, Laribi O, Leon-quinto T, Andreu E, Ripoll C and Soria B. 1998. Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor. FASEB J. 12: 1341–1348.

53. Peschke E, Peschke D, Hammer T and Csernus V. 1997. Influence of melatonin and serotonin on glucose-stimulated insulin release from perifused rat pancreatic islets in vitro. J Pineal Res. 23: 156–163

54. Kulkarni RN, Wang ZL, Wang RM, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JV, Bailey CJ and Bloom SR. 1997. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest. 100: 2729–2736.

55. Guler HP, Schmid C, Zapf J and Froesch ER. 1989. Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. Proc Natl Acad Sci U S A. 86: 2868–2872.

56. Cañas X, Fernández-López JA, Ardévol A, Adán C, Esteve M, Rafecas I, Remesar X and Alemany M. 1995. Rat insulin turnover in vivo. Endocrinology. 136: 3871-3876.

57. Sato H, Terasaki T, Mizuguchi H, Okumura K and Tsuji A. 1991. Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver. Diabetologia. 34: 613-621.

58. Duckworth WC, Bennett RG and Hamel FG. 1998. Insulin degradation: progress and potential. Endocr Rev. 19: 608-624.

59. Rabkin R, Ryan MP and Duckworth WC. 1984. The renal metabolism of insulin. Diabetologia. 27: 351-357.

60. Hamel FG, Peavy DE, Ryan MP and Duckworth WC. 1987. HPLC analysis of insulin degradation products from isolated hepatocytes. Effects of inhibitors suggest intracellular and extracellular pathways. Diabetes. 36: 702-708.

Insulina. Estructura, síntesis, secreción, depuración y degradación (Revisión)
Estructura de la insulina
Biosíntesis de la insulina.
Regulación de la síntesis de insulina
Secreción de insulina

NOTA: Toda la información que se brinda en este artículo es de carácter investigativo y con fines académicos y de actualización para estudiantes y profesionales de la salud. En ningún caso es de carácter general ni sustituye el asesoramiento de un médico. Ante cualquier duda que pueda tener sobre su estado de salud, consulte con su médico o especialista.

Instituto de Medicina Tropical - Facultad de Medicina - Universidad Central de Venezuela.
Elaborado por el Centro de Análisis de Imágenes Biomédicas Computarizadas CAIBCO,
Este portal ha sido desarrollado gracias al apoyo del Fonacit