Insulin partially reverses deficits in peripheral nerve blood flow and conduction in experimental diabetes

Abstract

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.

Effect of Endurance Exercise on Myosin Heavy Chain Isoform Expression in Diabetic Rats with Peripheral Neuropathy

“…Insulin is known to inhibit protein catabolism 23 and to improve peripheral nerve conduction velocity, nerve blood flow, and axonal transport in diabetic rats. 16,33 Therefore, small amounts of insulin may have beneficial effects on muscle distinct from decreasing hyperglycemia.…”

Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes

“…From a metabolic perspective, experimental diabetes in rats (model for Type 1 diabetes that causes chronic, severe hyperglycemia ϳ20 -40 mmol/l) results in increased nerve glucose, fructose, polyols, aldose reductase activity, protein kinase C activity, and monoenzymatic protein glycosylation as well as a reduction in nerve myoinositol and sodium potassium ATPase activity (13,15,29,32,51,63). From a vascular perspective, experimental diabetes is linked with reduced endothelial function (37, 50) and nerve blood flow (10,16,36,40,43,50,64). Together, these factors contribute to nerve dysfunction (10,16,40,64).…”

Direct Insulin Signaling of Neurons Reverses Diabetic Neuropathy

“…Work in experimental models and in humans has demonstrated correction or prevention of polyneuropathy in diabetic subjects treated with insulin infusions to render euglycemia (2)(3)(4). Implicit in these studies, however, has been the assumption that prevention of neuropathy is exclusively an indirect benefit of insulin's actions on glycemia.…”