Insulin partially reverses deficits in peripheral nerve blood flow and conduction in experimental diabetes.
Decreased nerve blood flow may be a pathogenetic factor in diabetic neuropathy. Previously it was shown that insulin treatment, commenced at the onset of streptozotocin-diabetes, prevents the development of a nerve blood flow deficit in the diabetic rat. The present study sought to determine the effect of short-term (one month) and acute (one hour) insulin reversal treatment on nerve blood flow deficits in streptozotocin-diabetes. Sciatic nerve blood flow was assessed using laser Doppler flowmetry. Treatment was initiated after one month of diabetes. One month of reversal insulin treatment ameliorated nerve laser Doppler flux (NDF) deficits; in untreated diabetic rats NDF was 51% of that in control animals (P < 0.01), in insulin-treated diabetic rats NDF was 85% of control values (P < 0.01 vs. untreated diabetic, P < 0.05 vs. control). In association with blood flow increases, we found a significant amelioration of motor (P < 0.05 vs. untreated diabetic) and sensory (P < 0.01 vs. untreated diabetic) nerve conduction velocities but not of exaggerated resistance to hypoxic conduction block. Insulin partially reversed hyperglycaemia and sciatic nerve polyol and sugar levels. In a second experiment, in rats with one month of diabetes, acute infusion of insulin led to a 47% (P < 0.001 vs. pre-insulin values) reduction of plasma glucose. This fall in plasma glucose was accompanied by a 38% (P < 0.05 vs. pre-insulin values) increase in NDF. Sensory nerve conduction velocity was marginally increased (6%, P < 0.05 vs. pre-insulin values) after insulin infusion, but motor conduction velocity was not. The data indicate that insulin can partially reverse deficits in nerve blood flow and conduction in diabetic rats.
Biessels
G J
GJ
William Harvey Research Institute, Department of Pharmacology, Queen Mary and Westfield College, London, UK.
Stevens
E J
EJ
Mahmood
S J
SJ
Gispen
W H
WH
Tomlinson
D R
DR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin