Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats with experimental diabetes; effects of insulin and aldose reductase inhibition.
This study was designed to determine whether deficient substance P in the sciatic nerve of diabetic rats was associated with a similar reduction in calcitonin gene-related peptide and whether the depletion of either or both peptides could be affected by insulin treatment or by aldose reductase inhibition. Substance P and calcitonin gene-related peptide were measured as immunoreactivities in the same nerve extracts. The sciatic nerve content of substance P was significantly reduced in diabetic rats (0.063 +/- 0.011; all data are mean +/- 1 standard deviation in ng peptide/mg nerve protein; n = 9 for all groups) compared to controls (0.093 +/- 0.026). The calcitonin gene related peptide content was similarly reduced (2.14 +/- 0.49) compared to controls (3.78 +/- 1.21). Tight glycaemic control with insulin prevented completely the deficit in both peptides (substance P = 0.096 +/- 0.021, calcitonin gene-related peptide = 4.66 +/- 0.92). Treatment with the aldose reductase inhibitor, imirestat, corrected the substance P deficit (0.08 +/- 0.018) and attenuated the calcitonin gene-related peptide (3.55 +/- 1.03) depletion seen in the untreated diabetic animals. This indicates that the polyol pathway may play a role in the peptide status of the sciatic nerve. Regression analysis of all data gave r2 = 0.53, indicating a comparable effect of diabetes and the treatments on both peptides.
Diemel
L T
LT
Department of Pharmacology, Queen Mary and Westfield College, London, UK.
Stevens
E J
EJ
Willars
G B
GB
Tomlinson
D R
DR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005449:Fluorenes / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006827:Hydantoins / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism; D013373:Substance P / Q000172:deficiency*
D001786:Blood Glucose; D005449:Fluorenes; D006827:Hydantoins; D007328:Insulin; C052241:imirestat; D005632:Fructose; D013373:Substance P; D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide