Major Interest:
Chronic complications in diabetes, Non-Alzheimer senile dementias.

Research and Professional Experience:
1974-83 Assistant Professor, Department of Pathology, University of Goteborg, Sweden
1978-81 Assistant Professor, Dept. of Pathology, University of Toronto, Toronto, Ontario, Canada
1981-82 Associate Professor, Dept. of Pathology, University of Toronto, Toronto, Ontario, Canada
1982-85 Associate Professor, Head, Sec. of Neuropathol., Dept. of Pathol., Univ. of Manitoba, Winnipeg, Canada
1985-90 Professor and Head (GFT), Section of Neuropathology, University of Manitoba, Canada
1988-90 Director, Diabetes Research Centre, University of Manitoba, Winnipeg, Canada
1990-96 Professor, Department of Pathology, University of Michigan, Ann Arbor, MI, USA
1991-96 Professor, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
1992-00 Director, Neuropathology Core, Michigan Alzheimer Disease Research Center, University of Michigan, Ann Arbor, MI, USA
1996-99 Visiting Professor, Department of Pathology, University of Michigan, Ann Arbor, MI, USA
1996-pres Professor of Pathology, Wayne State University, Detroit, MI, USA
1996-pres Professor of Neurology, Wayne State University, Detroit, MI, USA
2000-2002 Director, WSU Morris Hood Jr Comprehensive Diabetes Center, Detroit, MI, USA

Honors And Awards:
Chinese Academy of Medicine's Award for Academic Achievement, Beijing, 1981 Award for Academic Achievement, Tohoku Medical Society, Sendai, Japan, 1985 Prezzo d'ora, Consiglio Nationale delle Riccerche, Rome, Italy, 1987 Royal College Lecturer, Toronto, Ontario, Canada, 1990 Royal College Lecturer, London, UK 1993 Distinguished Scientists Award, Pfizer, Groton, CT, 1996 One of the 2000 most Outstanding Scientists of the 20th Century, University of Cambridge, UK, 1999 International Order of Merit, UK 1999 Order of International Ambassadors, USA 1999 Honorary External Director, International Diabetes Health Center, Scotsdale, AZ, 2001 Nicolae Paulescu Award, Bucharest, 2002 Honorary Doctorate, University of Bucharest, Romania, 2002

Editorial Positions:
1995-pres Co-Editor, Morphometry in Biomedical Sciences, McMillan
1997-pres Editor-in-Chief, (Founding Editor), Frontiers in Animal Diabetes Research
1997-pres Editor-in-Chief (Founding Editor), Journal of Experimental Diabetes Research
1998-pres Co Editor, Diabetes Metabolism Research and Reviews
1999-pres Executive Editor, Health and Medicine, McMillan

Publications:
Publications (selected from total of 826 publications; 284 peer-reviewed papers; 87 book chapters; 16 book edits; 439 abstracts) Peer-Reviewed Papers:

1. Sundkvist G, Dahlin L-B, Eriksson KF, Lindgärde F, Rosén I, Lattimer SA, Sima AAF, Greene DA: Sorbitol levels and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance. Diab Med 17:259-268, 2000.

2. Sima AAF, Zhang W, Xu G, Sugimoto K, Guberski DL, Yorek MA: A comparison of diabetic polyneuropathy in type-2 diabetic BBZDR/Wor-rat and in type 1 diabetic BB/Wor-rat. Diabetologia 43:786-793, 2000.

3. Sugimoto K, Murakawa Y, Zhang W-X, Xu G, Sima AAF: Insulin receptor in rat peripheral nerve: its localization and alternatively spliced isoforms. Diab/Metab Res Rev 16(5):354-63, 2000.

4. Felice KJ, Gomez-Lira M, Natowicz M, Grunnet ML, Tsongalis G, Sima AAF, Kaplan RF: Adult-onset metachromatic leucodystrophy: a novel mutation in the arylsulfatase A gene associated with an isolated polyneuropathy. Neurology 55(7):1036-39, 2000.

5. Kluin KJ, Gilman S, Foster NL, Sima AAF, D’Amato C, Bruch LA, Bluemlein RN, Little R, Johanns J: Neuropathologic correlates of dysarthria in PSP. Arch. Neurology 58:265-269, 2001.

6. Li Z-G, Qiang X, Sima AAF, Grunberger G: C-peptide attenuates protein tyrosine phosphatase activity and enhances glycogen synthesis in L6 myoblasts. Biochem Biophys Res Com 26:615-619, 2001.

7. Loeffler DA, Sima AAF, LeWitt PA: Ceruloplasmin Immunoreactivity in Neurodegenerative Disorders. Free Radical Res 35(2):111-8, 2001.

8. Clark L., Foster N., Sima AAF, Williamson K: A survey of polymorphisms and mutations in the microtubule – associated protein tau gene in sporadic fronto-temporal dementia and progressive supranuclear palsy. Am. J. Hum. Genetics 15:767-778, 2001.

9. Sima AAF, Grunberger G, Jörnvall H, Wahren J and the C-peptide Study Group: Proinsulin C-peptide – A consensus statement. Internatl. J. Exp. Diab. Res 2:145-151, 2001.

10. Minoshima S, Foster NL, Sima AAF, Frey KA, Albin RL, Kuhl DE: Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol 50(3):358-65, 2001.

11. Hall KE, Liu J, Sima AAF, Wiley JW: Impaired inhibitory G protein function contributes to increased calcium currents in rats with diabetic neuropathy. J Neurophysiol 86(2):760-70, 2001.

12. Sima AAF, Zhang W-X, Sugimoto K, Henry D, Li Z-G, Wahren J, Grunberger G: C-peptide prevents and improves chronic type 1 diabetic neuropathy in the BB/Wor-rat. Diabetologia 44:889-897, 2001.

13. Grunberger G, Qiang X, Li Z-G, Mathews ST, Sbriessa D, Shisheva A, Sima AAF: Molecular basis for the insulinomimetic effects of C-peptide. Diabetologia 44:1247-1257, 2001.

14. Xu G and Sima AAF: Altered immediate early gene expression is impaired in diabetic nerve: Implications in regeneration. J. Neuropath. Exp. Neurology 60(10):972-83, 2001.

15. Zhang W, Yorek M, Pierson CR, Murakawa Y, Breidenbach A, Sima AAF: Human C-peptide dose dependently prevents early neuropathy in the BB/Wor-rat. Internatl. J. Exp. Diab. Res. 2(3):187-194, 2001.

16. Lynch T, Sano M, Marder KS, Bell KL, Foster NL, Defendini RF, Sima AAF, Keohane C, Nygaard TG, Fahn S, Mayeux R, Rowland LP, Wilhelmsen KC: Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. In 50th AnniversaryReprint Collection: Parkinson’s Disease. Jankovic J (ed). Neurology 57(Suppl 3) 539-45, 2001.

17. Foster NL, Son EJ, Moura V, Gelb DJ, Sima AAF: Spontaneous extrapyramidal signs occur in both dementia with Lewy bodies and Alzheimer’s disease. Arch Neurol 59:256-262, 2001.

18. Zhang W, Murakawa Y, Wozniak KM, Slusher B, Sima AAF: GCPII (NAALADase) inhibition prevents long-term diabetic neuropathy in type 1 diabetic BB-Wor-rat. J Neurol Science 194:21-28, 2002.

19. Xu G, Murakawa Y, Pierson CR, Sima AAF: Altered ß-tubulin and neurofilament expression and impaired axonal growth in diabetic nerve regeneration. J. Neuropath Exp Neurol 61:164-175, 2002.

20. Sugimoto K, Murakawa Y, Sima AAF: Expression and localization of insulin receptor in rat dorsal root ganglion and spinal cord. JPNS 7:44-53, 2002.

21. Murakawa Y, Zhang W, Pierson CR, Brismar T, Östenson C-G, Efendric S, Sima AAF: Impaired glucose tolerance and insulinopenia in the GK-rat causes peripheral neuropathy. Diab Metab Res Rev 18:473-483, 2002.

22. Li Z, Zhang W, Grunberger G, Sima AAF: Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 946:212-231, 2002.

23. Pierson CR, Zhang W, Murakawa Y, Sima AAF: Early gene responses of trophic factors differ in nerve regeneration in type 1 and type 2 diabeticneuropathy. J. Neuropath. Exp. Neurol. 61:857-871, 2002.

24. Li Z-G, Zhang W, Sima AAF: C-peptide prevents hippocampal apoptosis in type 1 diabetes. Int. J. Exp. Diab. Res. 3:241-246, 2002.

25. Lahiri DK, Kotwal GJ, Farlow MR, Sima AAF, Kupsky W, Sarkar FH, Sambamurti K: The role of the carboxyl-terminal fragments of amyloid precursor protein in Alzheimer’s disease. Ann NY Acad Sci 973:334-339, 2002.

26. Sima AAF: Nuove evidenze cliniche sul ruolo di L-acetylcarnitina: resultati di uno studio randomizzato multicentrico internationale su oltre 1300 pazienti con neuropatia diabetica. In: Nuove frontiere nel trattomento del dolore neuropatico. Canonico PL, Rossi F (eds), Sin Napoli, 16:161-167, 2002.

27. Pierson CR, Zhang W, Murakawa Y, Sima AAF: Tubulin and neurofilament expression and axonal growth differ in type 1 and type 2 diabetic polyneuropathy. J Neuropath Exp Neurology, 62:260-271, 2003.

28. Pierson CR, Zhang W, Sima AAF: Proinsulin C-peptide replacement in type 1 diabetic BB/Wor-rats prevents deficits in nerve fiber regeneration. J Neuropath Exp Neurology 62:765-779, 2003.

29. Li Z-G, Zhang W., Sima AAF: C-peptide enhances insulin-mediated cell growth and protection against high glucose induced apoptosis in SH-SY5Y cells. Diab. Metab. Res. Rev. 19:375-385, 2003. Editorial: Wahren J: C-peptide makes a comeback. Diab. Metab. Res. Rev. 19:345-347, 2003.

30. Sima AAF: New insights into the metabolic and molecular basis for diabetic neuropathy. Cell Mol. Life Sci. 60:2445-2464, 2003.

31. Sima AAF: C-peptide and diabetic neuropathy. Expert Opin. Investig. Drugs 12:1471-1488, 2003.

32. Sima AAF, Amato A, Calvani M, Fiskum G, Scapagnini G: Diabetic neuropathy and oxidative stress. J. Clin. Invest., Aug. 12, 2003; http://www.jci.org/cgi/eletters/111/4/431.

33. Sima AAF, Li Z-G, Zhang W: The IGF system and neurological complications in diabetes. Exp. Diab. Res., 4:235-256, 2003.

34. Sima AAF: Neurotrophism and Cytokines in Diabetic Complications. Exp. Diab. Res. 4:1, 2003.

35. Sima AAF: Diabetic neuropathy in type 1 and type 2 diabetes and the effects of C-peptide. Neurol. Sci. 220:133-136, 2004.

36. Sima AAF: Preface to Physiological and Pathophysiological significance of C-peptide Actions. Exp. Diab. Res. 5:1-2, 2004.

37. Chakrabarti S, Khan ZA, Zhang W, Sima AAF: C-peptide and retinal microangiopathy in diabetes. Exp. Diab. Res., 5:91-96, 2004.

38. Li ZG, Sima AAF: C-peptide and CNS complications in diabetes. Exp. Diab. Res., 5:79-90, 2004.

39. Li H, Xu L, Dunbar JC, Dhabuwala CB, Sima AAF: Effects of C-peptide on expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in human cavernosal smooth muscle cell. J. Urol. 64:622-627, 2004.

40. Sima AAF, Zhang W, Grunberger G: Type 1 diabetic neuropathy and C-peptide. Exp. Diab. Res., 5:65-78, 2004.

41. Grunberger G, Sima AAF: The C-peptide signaling. Exp. Diab. Res., 5:25-36, 2004.

42. Sima AAF, Kamiya H, Li Z-G: Insulin, C-peptide hyperglycemia and central nervous system complications in diabetes. Europ J Pharmacology, 490:187-197, 2004.

43. Schmidt RE, Dorsey DA, Beaudet LN, Parvin CA, Zhang W, Sima AAF: Experimental rat models of type 1 and type 2 diabetes differ in sympathetic neuronal dystrophy. J. Neuropath. Exp. Neurol. 63:450-460, 2004.

44. Smith HS, Sima AAF: Keeping the insulin-like growth factor system in harmony. J Neuropath Pain (in press).

45. Sima AAF: Neuropathology of diabetic neuropathic pain. J. Neuropath. Pain (in press).

46. Sima AAF: Zhang W., Li Z-G, Murakawa Y, Pierson CR:. Molecular alterations underlie nodal and paranodal degeneration in type 1 diabetic neuropathy and are prevented by C-peptide. Diabetes 53:1556-1563, 2004.

47. Stevens MJ, Zhang W, Li F, Sima AAF: C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor-rats. Am. J. Physiol. 287:E497-505, 2004.

48. Sima AAF: Kamiya H: Insulin, C-peptide and diabetic neuropathy. Science Med. 10:308-319, 2004.

49. Sima AAF: Will C-peptide substitution make a difference in combating complications in insulin deficient diabetes? Rev. Diab. Studies 1:55-57, 2004 (Editorial).

50. Sima AAF: Diabetes underlies common neurological disorders. Ann Neurol. 56:459-461, 2004 (Editorial).

51. Kamiya H, Zhang W, Sima AAF: C-peptide prevents nociceptive sensory neuropathy in type 1 diabetes. Ann. Neurol. (in press).

52. Sima AAF, Calvani M, Mehra M, Amato A: Acetyl-L-carnitine improves pain, vibratory perception and nerve morphology in patients with chronic diabetic peripheral neuropathy: an analysis of two randomized, placebo-controlled trials. Diabetes Care (in press).

53. Sima AAF: Pathological mechanisms involved in diabetic neuropathy. Can we slow the process? Curr Opin Drug Develop (in press).

54. Li ZG, Britton M, Sima AAF, Dunbar J: Diabetes enhances apoptosis induced by cerebral ischemia. Life Sci 76:249-262, 2004.

Articles Submitted for Publication:

Zhang W, Slusher B, Wozniak KM, Tsukamoto T, Sima AAF: NAALADase inhibition improves long-term diabetic neuropathy in type 1 diabetes. J. Neurolog. Sci. (submitted).

Kamiya H, Murakawa Y, Zhang W, Sima AAF: Sensory nociceptive neuropathy differs in type 1 and type 2 diabetes. Diab. Metab. Res. Rev. (submitted).

Li Z-G, Zhang W, Sima AAF: The role of impaired insulin/IGF action in primary diabetic encephalopathy. Brain Res. (submitted).

Sima AAF, Li Z-G: The effect of C-peptide on cognitive dysfunction and hippocampal apoptosis in type 1 diabetes. Diabetes (submitted).

e-mail: asima@med.wayne.edu