The Role of Glycation in the Pathogenesis of Diabetic Polyneuropathy

Overview

Journal Mol Pathol

Specialty Molecular Biology

Date 2001 Nov 29

PMID 11724915

Citations 24

Authors

R H King

Affiliations

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Abstract

The most common neuropathy associated with diabetes mellitus is a distal sensory polyneuropathy. The relative importance of the direct effects of prolonged glycaemia on nervous tissue compared with indirect damage resulting from changes in blood vessels is not known. Although the importance of glycaemia is confirmed by a study showing that the incidence of neuropathy is greatly reduced by strict glycaemic control, many of the details of the deleterious effects of glycaemia on the peripheral nervous system (PNS) are not understood. These may be the result of direct damage to any of the cells in the PNS or the disruption of neuronal metabolism, axonal transport mechanisms, or repair capabilities; in addition, they may result from the effects of glycation on PNS connective tissue or a combination of some or all of the above mentioned mechanisms. The relative importance of these various mechanisms by which diabetes damages the PNS is a matter of conjecture. Therapeutic approaches targeting a specific mechanism such as those utilising aldose reductase inhibitors, or advanced glycation endproduct inhibitors have met with limited success. Clearly, it is difficult to design a treatment for diabetic neuropathy while its pathogenesis is still poorly understood.

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References

Woolf C, Reynolds M, Molander C, OBrien C, Lindsay R, Benowitz L . The growth-associated protein GAP-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury. Neuroscience. 1990; 34(2):465-78. DOI: 10.1016/0306-4522(90)90155-w. View

Williams S, Howarth N, Devenny J, Bitensky M . Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus. Proc Natl Acad Sci U S A. 1982; 79(21):6546-50. PMC: 347164. DOI: 10.1073/pnas.79.21.6546. View

Mendell J, Sahenk Z, Warmolts J, Marshall J, Thibert P . The spontaneously diabetic BB Wistar rat. Morphologic and physiologic studies of peripheral nerve. J Neurol Sci. 1981; 52(1):103-15. DOI: 10.1016/0022-510x(81)90139-8. View

Bradley J, King R, Muddle J, Thomas P . The extracellular matrix of peripheral nerve in diabetic polyneuropathy. Acta Neuropathol. 2000; 99(5):539-46. DOI: 10.1007/s004010051158. View

Vlassara H, Brownlee M, Cerami A . Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. Proc Natl Acad Sci U S A. 1981; 78(8):5190-2. PMC: 320369. DOI: 10.1073/pnas.78.8.5190. View

Pekiner C, Cullum N, Hughes J, Hargreaves A, Mahon J, Casson I . Glycation of brain actin in experimental diabetes. J Neurochem. 1993; 61(2):436-42. DOI: 10.1111/j.1471-4159.1993.tb02143.x. View

Nathan D, Genuth S, Lachin J, Cleary P, Crofford O, Davis M . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14):977-86. DOI: 10.1056/NEJM199309303291401. View

Yanagida H, Tanaka J, Maruo S . Immunocytochemical localization of a cell adhesion molecule, integrin alpha5beta1, in nerve growth cones. J Orthop Sci. 1999; 4(5):353-60. DOI: 10.1007/s007760050116. View

King R, Llewelyn J, Thomas P, Gilbey S, Watkins P . Diabetic neuropathy: abnormalities of Schwann cell and perineurial basal laminae. Implications for diabetic vasculopathy. Neuropathol Appl Neurobiol. 1989; 15(4):339-55. DOI: 10.1111/j.1365-2990.1989.tb01234.x. View

10.

Sarthy P, Fu M . Localization of laminin B1 mRNA in retinal ganglion cells by in situ hybridization. J Cell Biol. 1990; 110(6):2099-108. PMC: 2116127. DOI: 10.1083/jcb.110.6.2099. View

11.

Brownlee M . Glycation products and the pathogenesis of diabetic complications. Diabetes Care. 1992; 15(12):1835-43. DOI: 10.2337/diacare.15.12.1835. View

12.

Lorenzi M, Montisano D, Toledo S, Barrieux A . High glucose induces DNA damage in cultured human endothelial cells. J Clin Invest. 1986; 77(1):322-5. PMC: 423344. DOI: 10.1172/JCI112295. View

13.

NATHANIEL E . PEASE DC: DEGENERATIVE CHANGES IN RAT DORSAL ROOTS DURING WALLERIAN DEGENERATION. J Ultrastruct Res. 1963; 52:511-32. DOI: 10.1016/s0022-5320(63)80082-9. View

14.

Anderson S, Kim Y, Tsilibary E . Effects of matrix glycation on mesangial cell adhesion, spreading and proliferation. Kidney Int. 1994; 46(5):1359-67. DOI: 10.1038/ki.1994.405. View

15.

Brownlee M . Lilly Lecture 1993. Glycation and diabetic complications. Diabetes. 1994; 43(6):836-41. DOI: 10.2337/diab.43.6.836. View

16.

Klein D, Oegema Jr T, Brown D . Release of glomerular heparan-35SO4 proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats. Diabetes. 1989; 38(1):130-9. DOI: 10.2337/diab.38.1.130. View

17.

Fu M, Requena J, Jenkins A, Lyons T, Baynes J, Thorpe S . The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem. 1996; 271(17):9982-6. DOI: 10.1074/jbc.271.17.9982. View

18.

Skene J, Virag I . Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43. J Cell Biol. 1989; 108(2):613-24. PMC: 2115450. DOI: 10.1083/jcb.108.2.613. View

19.

Graham A, Johnson P . Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy. Ann Neurol. 1985; 17(5):450-4. DOI: 10.1002/ana.410170506. View

20.

Monnier V, Kohn R, Cerami A . Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci U S A. 1984; 81(2):583-7. PMC: 344723. DOI: 10.1073/pnas.81.2.583. View