View More View Less
  • 1 Fővárosi Önkormányzat Szent János Kórház és Észak-budai Egyesített Intézményei II. Belgyógyászati Osztály Budapest
  • 2 Fővárosi Önkormányzat Károlyi Sándor Kórház I. Belgyógyászati Osztály Budapest
  • 3 Semmelweis Egyetem, Általános Orvostudományi Kar Munka- és Környezet-egészségtani Tanszék Budapest
Open access

A zsírszövetben az inzulinreceptor jelátviteli folyamatait auto-, para- és endokrin hatásokkal szabályozó számos fehérje termelődik és szekretálódik. Ezek közül több, így a tumornekrózis-faktor-α és szolúbilis receptor formái, az sTNFR1 és sTNFR2, a rezisztin, retinolkötő fehérje-4, plazminogénaktivátor-inhibitor, lipokain-1 gátolja az inzulin jelátviteli folyamatait és inzulinrezisztenciát okoz, elsősorban a zsírszövetben, a májban, az izomszövetben, az agyban, az endothelsejtekben, valamint a hasnyálmirigy β-sejtjeiben. Más fehérjék, így az adiponektin, visfatin, vaspin, omentin, apelin és chemerin pedig javítják az inzulinreceptor jelátvitelét. Az összefoglalás áttekinti az inzulinreceptor jelátviteli folyamatainak főbb részleteit és kitér az elhízásban, valamint a 2-es típusú cukorbetegségben észlelhető inzulin- és citokinrezisztenciák patomechanizmusában a közelmúltban megismert molekuláris tényezőkre (például a suppressor of cytokine signaling fehérje család).

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Goldfine, I. D., Maddux, B. A., Youngren, J. F. és mtsai: The role of membrane glycoprotein PC-1/ENPP1 in the pathogenesis of insulin resistance and related abnormalities. Endocr. Rev., 2008, 29 , 62–75.

    Youngren J. F. , 'The role of membrane glycoprotein PC-1/ENPP1 in the pathogenesis of insulin resistance and related abnormalities ' (2008 ) 29 Endocr. Rev. : 62 -75.

    • Search Google Scholar
  • Winkler G., Cseh K.: Az inzulinrezisztencia zsírszöveti tényezői. Diabetol. Hung. In press.

  • White, F. M.: Insulin signaling in health and disease. Science, 2003, 302 , 1710–1711.

    White F. M. , 'Insulin signaling in health and disease ' (2003 ) 302 Science : 1710 -1711.

  • Li, C., Zhang, B. B.: Insulin signaling and action: glucose, lipids, protein. http:// www.endotext.org/Diabetes/diabetes4/diabetes2.html

  • Ottensmeyer, F. P., Beniac, D. R., Luo, RZ-T. és mtsa: Mechanism of transmembrane signaling: insulin binding and the insulin receptor. Biochemistry, 2000, 39 , 12103–12112.

    Luo RZ-T. , 'Mechanism of transmembrane signaling: insulin binding and the insulin receptor ' (2000 ) 39 Biochemistry : 12103 -12112.

    • Search Google Scholar
  • Temofonte, N., Sajan, M. P., Nimal, S. és mtsai: Combined thiazolidinedione-metformin treatment synergistically improves insulin signalling to insulin receptor substrate-1-dependent phosphatidylinositol 3-kinase, atypical protein kinase C and protein kinase B/Akt in human diabetic muscle. Diabetologia, 2009, 52 , 60–64.

    Nimal S. , 'Combined thiazolidinedione-metformin treatment synergistically improves insulin signalling to insulin receptor substrate-1-dependent phosphatidylinositol 3-kinase, atypical protein kinase C and protein kinase B/Akt in human diabetic muscle ' (2009 ) 52 Diabetologia : 60 -64.

    • Search Google Scholar
  • Lebrun, P., van Obberghen, E.: SOCS in insulin signaling. Acta Physiol., 2008, 192 , 29–36.

    Obberghen E. , 'SOCS in insulin signaling ' (2008 ) 192 Acta Physiol. : 29 -36.

  • King, M. W.: AMP activated protein kinase, AMPK. http://themedicalbiochemistrypage.org 2009

  • Cseh K., Winkler G.: A zsírszöveti „endokrin” szabályozó rendszer és szerepe az inzulinrezisztencia kialakulásában. In Halmos T., Jermendy, Gy. (szerk.): Diabetes mellitus. Elmélet és klinikum. Medicina Kiadó, Budapest, 2002, 98–112.

    Winkler G. , '', in Diabetes mellitus. Elmélet és klinikum , (2002 ) -.

  • Behre, C. J.: Adiponectin, obesity and atherosclerosis. Scand J. Clin. Lab. Invest., 2007, 67 , 449–458.

    Behre C. J. , 'Adiponectin, obesity and atherosclerosis ' (2007 ) 67 Scand J. Clin. Lab. Invest. : 449 -458.

    • Search Google Scholar
  • Menzaghi, C., Trischitta, V., Doria, A.: Genetic influences of adiponectin on insulin resistance, type 2 diabetes and cardiovascular disease. Diabetes, 2007, 56 , 1198–1209.

    Doria A. , 'Genetic influences of adiponectin on insulin resistance, type 2 diabetes and cardiovascular disease ' (2007 ) 56 Diabetes : 1198 -1209.

    • Search Google Scholar
  • Kadowaki, T., Yamauchi, T., Kubota, N.: The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Letters, 2008, 582 , 74–80.

    Kubota N. , 'The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS ' (2008 ) 582 FEBS Letters : 74 -80.

    • Search Google Scholar
  • Kubota, N., Yano, W., Kubota, T. és mtsai: Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab., 2007, 6 , 55–68.

    Kubota T. , 'Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake ' (2007 ) 6 Cell Metab. : 55 -68.

    • Search Google Scholar
  • Chehab, F. F.: Obesity and lipodystrophy – Where do the circles intersect? Endocrinology, 2008, 149 , 925–934.

    Chehab F. F. , 'Obesity and lipodystrophy – Where do the circles intersect? ' (2008 ) 149 Endocrinology : 925 -934.

    • Search Google Scholar
  • Myers, M. G.: Leptin receptor signaling and regulation of mammalian physiology. Rec. Progr. Horm. Res., 2004, 59 , 287–304.

    Myers M. G. , 'Leptin receptor signaling and regulation of mammalian physiology ' (2004 ) 59 Rec. Progr. Horm. Res. : 287 -304.

    • Search Google Scholar
  • Brennan, A. M., Mantzoros, C. S.: Drug insight: the role of leptin in human physiology and pathophysiology – emerging clinical applications. Nat. Clin. Pract. Endocrinol. Metab., 2006, 2 , 318–327.

    Mantzoros C. S. , 'Drug insight: the role of leptin in human physiology and pathophysiology – emerging clinical applications ' (2006 ) 2 Nat. Clin. Pract. Endocrinol. Metab. : 318 -327.

    • Search Google Scholar
  • Jiang, L., Jia, Y., Yu, X. és mtsai: Tyrosine-dependent and -independent actions of leptin receptor in control of energy balance and glucose homeostasis. PNAS, 2008, 105 , 18619–18624.

    Yu X. , 'Tyrosine-dependent and -independent actions of leptin receptor in control of energy balance and glucose homeostasis ' (2008 ) 105 PNAS : 18619 -18624.

    • Search Google Scholar
  • Kassem, H. S., Arabi, A., Zantout, M. S. és mtsa: Negative effect of leptin on bone mass in type 1 diabetes. Acta Diabetol., 2008, 45 , 237–241.

    Zantout M. S. , 'Negative effect of leptin on bone mass in type 1 diabetes ' (2008 ) 45 Acta Diabetol. : 237 -241.

    • Search Google Scholar
  • Antuna-Puente, B., Fevec, B., Fellahi, S. és mtsa: Adipokines: the missing link between insulin resistance and obesity. Diabetes & Metabolism., 2008, 34 , 2–11.

    Fellahi S. , 'Adipokines: the missing link between insulin resistance and obesity ' (2008 ) 34 Diabetes & Metabolism. : 2 -11.

    • Search Google Scholar
  • Muse, E. D., Lam, T. K., Scherer, P. E. és mtsa: Hypothalamic resistin induces hepatic insulin resistance. J. Clin. Invest., 2007, 117 , 1670–1678.

    Scherer P. E. , 'Hypothalamic resistin induces hepatic insulin resistance ' (2007 ) 117 J. Clin. Invest. : 1670 -1678.

    • Search Google Scholar
  • Goralski, K. B., McCarthy, T. C., Hanniman, E. A. és mtsai: Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J. Biol. Chem., 2007, 282 , 28175–28188.

    Hanniman E. A. , 'Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism ' (2007 ) 282 J. Biol. Chem. : 28175 -28188.

    • Search Google Scholar
  • Bozaoglu, K., Bolton, K., McMillan, J. és mtsai: Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology, 2007, 148 , 4687–4694.

    McMillan J. , 'Chemerin is a novel adipokine associated with obesity and metabolic syndrome ' (2007 ) 148 Endocrinology : 4687 -4694.

    • Search Google Scholar
  • Takahashi, M., Takahashi, Y., Takahashi, K. és mtsai: Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Letters, 2008, 582 , 573–578.

    Takahashi K. , 'Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes ' (2008 ) 582 FEBS Letters : 573 -578.

    • Search Google Scholar
  • Yang, Q., Graham, T. E., Mody, N. és mtsai: Serum retinol binding protein-4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 2005, 436 , 356–362.

    Mody N. , 'Serum retinol binding protein-4 contributes to insulin resistance in obesity and type 2 diabetes ' (2005 ) 436 Nature : 356 -362.

    • Search Google Scholar
  • Graham, T. E., Yang, Q., Blüher, M. és mtsai: Retinol-binding protein-4 and insulin resistance in lean, obese and diabetic subjects. NEJM, 2006, 354 , 2552–2563.

    Blüher M. , 'Retinol-binding protein-4 and insulin resistance in lean, obese and diabetic subjects ' (2006 ) 354 NEJM : 2552 -2563.

    • Search Google Scholar
  • Youn, B.-S., Klöting, N., Kratzsch, J. és mtsai: Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes, 2008, 57 , 372–377.

    Kratzsch J. , 'Serum vaspin concentrations in human obesity and type 2 diabetes ' (2008 ) 57 Diabetes : 372 -377.

    • Search Google Scholar
  • Jenkins, A., Zhang, S. X., Gosmanova, A. és mtsai: Increased serum pigment epithelium-derived factor levels in type 2 diabetes. Diab. Res. Clin. Pract., 2008, 82 , E5–E7.

    Gosmanova A. , 'Increased serum pigment epithelium-derived factor levels in type 2 diabetes ' (2008 ) 82 Diab. Res. Clin. Pract. : E5 -E7.

    • Search Google Scholar
  • Ek, E. T. H., Dass, C. R., Choong, P. F. N.: Pigment epithelium-derived factor: a multimodal tumor inhibitor. Mol. Cancer Ther, 2006, 5 , 1641–1646.

    Choong P. F. N. , 'Pigment epithelium-derived factor: a multimodal tumor inhibitor ' (2006 ) 5 Mol. Cancer Ther : 1641 -1646.

    • Search Google Scholar
  • Adeghate, E.: Visfatin, structure, function and relation to diabetes mellitus and other dysfunctions. Curr. Med. Chem., 2008, 15 , 1851–1862.

    Adeghate E. , 'Visfatin, structure, function and relation to diabetes mellitus and other dysfunctions ' (2008 ) 15 Curr. Med. Chem. : 1851 -1862.

    • Search Google Scholar
  • Fukuhara, A., Matsuda, M., Nishizawa, M. és mtsai: A protein secreted by visceral fat that mimics the effects of insulin. Science, 2005, 307 , 426–430.

    Nishizawa M. , 'A protein secreted by visceral fat that mimics the effects of insulin ' (2005 ) 307 Science : 426 -430.

    • Search Google Scholar
  • Song, H. K., Lee, M. H., Kim, B. K. és mtsai: Visfatin: a new player in mesangial cell physiology and diabetic nephropathy. Am. J. Physiol. Renal. Physiol., 2008, 295 , F1485–F1494.

    Kim B. K. , 'Visfatin: a new player in mesangial cell physiology and diabetic nephropathy ' (2008 ) 295 Am. J. Physiol. Renal. Physiol. : F1485 -F1494.

    • Search Google Scholar
  • Gualillo, O., Gonzalez-Juanatey, J. R., Lago, F.: The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trend Cardiovasc. Med., 2007, 17 , 275–283.

    Lago F. , 'The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives ' (2007 ) 17 Trend Cardiovasc. Med. : 275 -283.

    • Search Google Scholar
  • Berndt, J., Klöting, N., Kralisch, S. és mtsai: Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes, 2005, 54 , 2911–2916.

    Kralisch S. , 'Plasma visfatin concentrations and fat depot-specific mRNA expression in humans ' (2005 ) 54 Diabetes : 2911 -2916.

    • Search Google Scholar
  • Wurm, S., Neumeier, M., Weigert, J. és mtsai: Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26) and adiponectin before and after oral glucose uptake in slim adults. Cardiovasc. Diabetol., 2007, 6 , 1–7. ( doi: 10.11186/1475-2840-6-7 )

    Weigert J. , 'Plasma levels of leptin, omentin, collagenous repeat-containing sequence of 26-kDa protein (CORS-26) and adiponectin before and after oral glucose uptake in slim adults ' (2007 ) 6 Cardiovasc. Diabetol. : 1 -7.

    • Search Google Scholar
  • de Souza Batista, C. M., Yang, R.-Z., Lee, N.-J. és mtsai: Omentin plasma levels and gene expression are decreased in obesity. Diabetes, 2007, 56 , 1655–1661.

    Lee N.-J. , 'Omentin plasma levels and gene expression are decreased in obesity ' (2007 ) 56 Diabetes : 1655 -1661.

    • Search Google Scholar
  • Reaux, A., DeMota, N., Skultetyova, I. és mtsai: Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain. J. Neurochemistry, 2001, 77 , 1085–1096.

    Skultetyova I. , 'Physiological role of a novel neuropeptide, apelin, and its receptor in the rat brain ' (2001 ) 77 J. Neurochemistry : 1085 -1096.

    • Search Google Scholar
  • Tan, B. K., Adya, R., Shan, X. és mtsai: Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine by insulin. Diabetes Care, 2009, 32 , 129–131.

    Shan X. , 'Ex vivo and in vivo regulation of lipocalin-2, a novel adipokine by insulin ' (2009 ) 32 Diabetes Care : 129 -131.

    • Search Google Scholar
  • Li, Y., Dowbenko, D., Lasky, L. A.: Caenorhabditis elegans PIAK, a phospholipid-independent kinase deactivates the Akt-PKB survival kinase. J. Biol. Chem., 2001, 276 , 20323–20329.

    Lasky L. A. , 'Caenorhabditis elegans PIAK, a phospholipid-independent kinase deactivates the Akt-PKB survival kinase ' (2001 ) 276 J. Biol. Chem. : 20323 -20329.

    • Search Google Scholar
  • Narbonne, P., Roy, R.: Caenorhabditis elegans dauers need LKB1/AMP to ration lipid reserves and ensure long term survival. Nature, doi:10.1038/nature07536 ; Published online 3 December 2008

    Roy R. , 'Caenorhabditis elegans dauers need LKB1/AMP to ration lipid reserves and ensure long term survival ' (2008 ) Nature : -.

    • Search Google Scholar