Clinical Autonomic Research

, Volume 5, Issue 3, pp 159–164 | Cite as

The effects of vasoactive intestinal polypeptide and substance P on methacholine-induced sweating and vascular flare in diabetic neuropathy

  • T. J. Berg
  • D. M. Levy
  • G. Reid
  • R. R. Abraham
Research Paper


Vasoactive intestinal polypeptide (VIP) and substance P (SP) immunoreactivity are reduced in the cutaneous nerves of diabetic patients with peripheral neuropathy. The functional significance of this finding was studied by measuring the forearm sweat response to intradermal methacholine and the effect of coadministration of VIP and SP in six normal subjects, and in six diabetic patients with neuropathy and eight without. Flare responses to the two peptides were also measured. Methacholine-induced sweat output was significantly greater in neuropathic patients compared with the other groups (p < 0.05), suggesting upper limb denervation supersensitivity. VIP and SP alone did not evoke sweating in any subject. Injection of VIP or SP reduced methacholine-induced sweating to a similar degree in all groups, except that the reduction was smaller in the nonneuropathic group than in the others (p = 0.028 versus normal subjects, p = 0.014 versus neuropathic diabetic patients). Flare responses to the peptides were markedly reduced in the neuropathic patients compared with the other groups (p < 0.01). In neuropathic patients, increased sweat responses and decreased flare coexist with diminished neurophysiological measurements; cutaneous sweating and flare responses provide valuable additional information to conventional methods of neurological assessment in diabetic neuropathy.


sweat gland substance P vasoactive intestinal polypeptide diabetic neuropathy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kennedy WR, Sakuta M, Sutherland D, Goetz FC. Quantitation of the sweating deficiency in diabetes mellitus.Ann Neurol 1984;15: 482–488.PubMedGoogle Scholar
  2. 2.
    Low P, Caskey PE, Tuck RR, Fealey RD, Dyck PJ. Quantitative sudomotor axon reflex test in normal and neuropathic subjects.Ann Neurol 1983;14: 573–580.PubMedGoogle Scholar
  3. 3.
    Ahmed M, LeQuesne PM. Quantitative sweat test in diabetic with neuropathic foot lesions.J Neurol Neurosurg Psychiat 1986;49: 1059–1062.PubMedGoogle Scholar
  4. 4.
    Aronin N, Leeman SE, Clements RS. Diminished flare responses in neuropathic diabetic patients.Diabetes 1987;36: 1139–1143.PubMedGoogle Scholar
  5. 5.
    Parkhouse N, Le Quesne PM. Impaired neurogenic vascular response in patients with diabetes and neuropathic foot lesions.N Engl J Med 1988;318: 1306–1309.PubMedGoogle Scholar
  6. 6.
    Lundberg JM, Hokfelt T, Uvnas-Wallensten K, Kohler C, Said SI. Occurrence of vasoactive intestinal polypeptide (VIP) -like immunoreactivity in certain cholinergic neurones of the cat: evidence from combined immunohistochemistry and acetylcholinesterase staining.Neuroscience 1979;4: 1539–1559.PubMedGoogle Scholar
  7. 7.
    Heinz-Erian P, Paul S, Said SI. Receptors for vasoactive intestinal peptide on isolated human sweat glands.Peptides 1986;7 (suppl. 1): 151–154.PubMedGoogle Scholar
  8. 8.
    Eedy DJ, Shaw C, Armstrong EP, Johnston CF, Buchanan KD. Vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in human eccrine sweat glands: demonstration of ínnervation, specific binding sites and presence in secretions.Br J Dermatol 1990;123: 65–76.PubMedGoogle Scholar
  9. 9.
    Yamashita Y, Imamura R, Ogawa T, Ohnishi T, Sugenoya J. Local effect of vasoactive intestinal peptide on human sweat-gland function.Jpn J Physiol 1987;37: 929–936.PubMedGoogle Scholar
  10. 10.
    Tanaka E, Uchiyama S, Nakano S. Effects of calcitonin gene-related peptide and vasoactive intestinal peptide on nicotine-induced sweating in man.J Auton Nerv Syst 1990;30: 265–268.PubMedGoogle Scholar
  11. 11.
    Landis SC, Fredieu JR. Coexistence of calcitonin gene-related peptide and vasoactive intestinal peptide in cholinergic sympathetic innervation of rat sweat glands.Brain Res 1986;377: 177–181.PubMedGoogle Scholar
  12. 12.
    Tainio H, Vaalasti A, Rechardt L. The distribution of SP, CGRP, galanin and ANP like immunoreactive nerves in human sweat glands.Histochem J 1987;19: 375–380.PubMedGoogle Scholar
  13. 13.
    Wallengren J, Ekman R, Sundler F. Occurrence and distribution of neuropeptides in the human skin.Acta Derm Venerol (Stockh) 1987;C7: 185–192.Google Scholar
  14. 14.
    Willars G, Calcutt NA, Compton AM, Tomlinson DR, Keen P. Substance P levels in peripheral nerve, skin, atrial myocardium and gastrointestinal tract of rat with long-term diabetes mellitus. Effects of aldose reductase inhibition.J Neurol Sci 1989;91: 153–164.PubMedGoogle Scholar
  15. 15.
    Levy DM, Karanth SS, Springall DR, Polak JM. Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study.Diabetologia 1989;32: 427–433.PubMedGoogle Scholar
  16. 16.
    Levy DM, Terenghi G, Gu X-H, Abraham RR, Springall DR, Polak JM. Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function.Diabetologia 1992;35: 889–897.PubMedGoogle Scholar
  17. 17.
    Levy DM, Abraham RR, Reid G. A comparison of two methods for testing thermal hresholds in diabetic neuropathy.J Neurol Neurosurg Psychiat 1989;52: 1072–1077.PubMedGoogle Scholar
  18. 18.
    Ewing DJ, Clarke BF. Autonomic neuropathy: its diagnosis and prognosis.Clin Endocrinol Metab 1986;15: 855–888.PubMedGoogle Scholar
  19. 19.
    Levy DM, Reid G, Abraham RR, Rowley DA. Assessment of basal and stimulated sweating in diabetes using a direct-reading computerized sudorometer.Diabetic Med 1991; 8 (symposium): S78-S81.PubMedGoogle Scholar
  20. 20.
    Low PA, Zimmerman BR, Dyck PJ. Comparison of distal sympathetic with vagal function in diabetic neuropathy.Muscle Nerve 1986;9: 592–596.PubMedGoogle Scholar
  21. 21.
    Levy DM, Rowley DA, Abraham RR. Changes in cholinergic sweat gland activation in diabetic neuropathy identified by computerised sweatspot analysis.Diabetologia 1991;34: 807–812.PubMedGoogle Scholar
  22. 22.
    Sato K, Sato F. Effect of VIP on sweat secretion and cAMP accumulation in isolated simian eccrine glands.Am J Physiol 1987;253 (RICP 22): R935-R941.PubMedGoogle Scholar
  23. 23.
    Torres NE, Zollman PJ, Low PA. Characterization of muscarinic receptor subtype of rat eccrine sweat gland by autoradiography.Brain Res 1991;550: 129–132.PubMedGoogle Scholar

Copyright information

© Rapid Science Publishers 1995

Authors and Affiliations

  • T. J. Berg
    • 1
  • D. M. Levy
    • 2
  • G. Reid
    • 3
  • R. R. Abraham
    • 4
  1. 1.Aker Diabetes Research UnitAker University HospitalOsloNorway
  2. 2.King's Diabetes CentreKing's College HospitalLondonUK
  3. 3.Sobell Department of NeurophysiologyInstitute of NeurologyLondonUK
  4. 4.London Diabetes and Lipid CentreLondonUK

Personalised recommendations