Summary:
Morphological and immunohistochemical studies in diabetic subjects have shown a depletion of the neuropeptide substance P (SP) in the central and peripheral nervous system. This is the first study investigating serum levels of substance P in type 1 diabetes patients (n = 50) and controls (n = 75) by means of an enzyme immunoassay. The serum level of SP was significantly decreased in the diabetic group compared to the control group (10.12 ± 0.29 vs. 12.25 ± 0.38 pg/ml; p < 0.0001). In diabetic patients, there was no correlation of substance P levels with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL-cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender. Furthermore, there was no difference in serum levels of SP in patients with or without retinopathy, but SP was significantly decreased in patients with neuropathy (9.59 ± 0.48 vs. 10.78 ± 0.83 pg/ml; p = 0.04).
These data show that SP is decreased in serum of type 1 diabetes patients, especially in those with diabetic neuropathy. Subsequent and already ongoing prospective studies in well validated diabetic patients with neuropathy may characterize the impact of this neurogenic marker in the course of diabetic neuropathy.
Abbreviations: SP = substance P; EIA = enzyme immunoassay; HDL = high density lipoprotein; LDL = low density lipoprotein
Key words:
Substance P - diabetes mellitus - serum level - neuropathy
References
-
1
Bloom S R, Polak J M, Laybourn P J, Najarian R C.
Regulatory peptides and the skin.
Clin Exp Dermatol.
8
3-18
1983;
-
2
Blumberg A, Bürgi W.
Behaviour of β2-microglobulin in patients with chronic renal failure undergoing hemodialysis, hemodiafiltration and continuous ambulatory peritoneal dialysis (CAPD).
Clin Nephrol.
27
245-249
1987;
-
3
Boden G, Master R W, Owen O E, Rudnick M R.
Human pancreatic polypeptide in chronic renal failure and cirrhosis of the liver: role of kidneys and liver in pancreatic polypeptide metabolism.
J Clin Endocrinol Metab.
51
573-578
1980;
-
4
Chang M M, Leeman S E, Nrall H D.
Amino acid sequence of substance P.
Nature.
232
86-87
1971;
-
5
Church M K, Lowman M A, Robinson C, Holgate S T, Benyon R C.
Interaction of neuropeptides with human mast cells.
Int Arch Allergy Appl Immunol.
88
70-78
1989;
-
6
Conlon J M, Deacon C F, Richter G, Stcökmann F, Creutzfeldt W.
Circulating tachykinins (substance P, neurokinin A, neuropeptide K) and the carcinoid flush.
Scand J Gastroenterol.
22
97-105
1987;
-
7
Dalsgaard C J, Johnsson C E, Hökfelt T, Cuello A C.
Localization of substance P-immunoreactive nerve fibers in the human digital skin.
Experientia.
39
1018-1020
1983;
-
8
Davidson W D, Springberg P D, Falkinburg N R.
Renal extraction and excretion of endogenous gastrin in dog.
Gastroenterology.
64
955-961
1973;
-
9
Eedy D J.
Neuropeptides in skin.
Br J Dermatol.
128
597-605
1993;
-
10
Hegbrant J, Thysell H, Ekman R.
Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment.
Scand J Urol Nephrol.
26
169-176
1992;
-
11
Kastrup J, Henriksen J H, Pedersen J H, Fahrenkrug J, Schaffalitzky de Muckadell O B, Schwartz T, Parving H H, Christensen N J.
Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide. substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients.
Clin Sci.
71
411-419
1986;
-
12
Katz A I, Rubenstein A H.
Metabolism of proinsulin, insulin and c-peptide in the rat.
J Clin Invest.
52
1113-1121
1973;
-
13
Levy D M, Karanth S S, Springall D R, Polak J M.
Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study.
Diabetologia.
32
427-433
1989;
-
14
Lindberger M, Schroder H D, Schultzberg M, Kristensson K, Persson A, Ostman J, Link H.
Nerve fiber studies in skin biosies in peripheral neuropathies. I. Immunohistichemical analysis of neuropeptides in diabetes mellitus.
J Neurol Sci.
93
289-296
1989;
-
15
Lysy J, Karmeli F, Goldin E.
Substance P levels in the rectal mucosa of diabteic patients with normal bowel function and constipation.
Scand J Gastroenterol.
28
49-52
1993;
-
16
Marshall K W, Chiu B, Inman R D.
Substance P and arthritis: analysis of plasma and synovial fluid levels.
Arthritis Rheum.
33
87-90
1990;
-
17
Mori K, Asakura S, Morokawa N, Takeyama M.
Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers.
J Pharm Pharmacol.
44
856-858
1992;
-
18
Said S I.
Vasoactive peptides. State-of-the-art review.
Hypertension
5
(Suppl 1)
I17-26
1983;
-
19
Saria A.
Neuropeptide.
Hautarzt.
43
745-752
1992;
-
20
Schaffalitzky de Muckadell O B, Aggestrup A, Stentoft P.
Flushing and substance P concentration during infusion of synthetic substance P in normal man.
Scand J Gastroenterol.
21
498-502
1986;
-
21
Schmidt R E, Dorsey D A, Roth K A.
Immunohistochemical characterization of NPY and substance P containing nerve terminals in aged and diabetic human sympathic ganglia.
Brain Res.
583
320-326
1992;
-
22
Snyder S H.
Brain peptides as neurotransmitters.
Science.
209
976-983
1980;
-
23
Tanio H, Vaalasti A, Rechardt L.
The distribution of substance P-, CGRP-, galanin- and ANP-like immunoreactive nerves in human sweat glands.
Histochem J.
19
375-380
1987;
-
24
Thysell H, Grubb A, Lindholm T, Ljunggren L, Martenson L.
Cystatin C: a new marker of biocompatibility or a good marker for the redistribution of LMW proteins during hemodialysis?.
Trans Am Soc Artif Intern Organs.
34
202-204
1988;
-
25
Valdemarsson S, Edvinsson L, Ekman R, Hedner P, Sjöholm A.
Increased level of substance P in patients with severe congestive heart failure treated with ACE inhibitors.
J Int Med.
230
325-331
1991;
-
26
Von Euler V S, Gaddum J H.
An unidentified depressor substance in certain tissue extracts.
J Physiol (London).
72
74-87
1931;
Dr. Thomas Kunt
Dept. of Internal Medicine and Endocrinology
Krankenhaus SÜW
Georg-Staab-Str. 3
D-76855 Annweiler
Phone: + 49-6346-970101
Fax: + 49-6346-970610
Email: endokrin@mail.uni-mainz.de