title: Insulin resistance occurs in parallel with sensory neuropathy in streptozotocin-induced diabetes in rats: differential response to early vs late insulin supplementation.
abstract: We investigated whether progressive sensory neuropathy was accompanied by changes in whole-body insulin sensitivity (WBIS) in rats made diabetic by streptozotocin (STZ). The effects of early and late insulin supplementation were also studied. The STZ-treated rats failed to gain weight and exhibited stable hyperglycemia and low plasma insulin levels with a decrease in nerve conduction velocity (NCV) measured in A and C fibers of the saphenous nerve. A decreased sensory neuropeptide (SNP) release such as that of substance P, somatostatin, and calcitonin gene-related peptide determined from organ fluid of tracheal preparations subjected to electrical field stimulation also occurred in diabetic animals. These features were accompanied by a decrease in WBIS measured by hyperinsulinemic-euglycemic glucose clamping and a decrease in insulin-stimulated glucose uptake in cardiac and gastrocnemius muscle. When insulin supplementation with slow-release implants (2 IU/d) was started 4 weeks after STZ injection, blood glucose level normalized. Both insulin sensitivity and sensory nerve function reflected in either NCV or SNP release completely recovered by the 12th post-STZ week. When the insulin implants were applied from the eighth post-STZ week, both WBIS and glucose uptake remained significantly decreased, with a seriously impaired NCV and SNP release with strong hyperglycemia. Late insulin supplementation, however, even by using double implantation from the 10th post-STZ week, was unable to restore blood glucose, WBIS, NCV, and SNP release by the 12th week. Insulin resistance occurs in parallel with sensory neuropathy in STZ-diabetic rats. Both can be improved by early but not late insulin supplementation.
authors.affiliation: Departments of Pharmacology and Pharmacotherapy, University of Debrecen, H-4032, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szilvássy
authors.forename: Joseph
authors.initials: J
authors.lastname: Németh
authors.forename: Péter
authors.initials: P
authors.lastname: Kovács
authors.forename: György
authors.initials: G
authors.lastname: Paragh
authors.forename: Réka
authors.initials: R
authors.lastname: Sári
authors.forename: László
authors.initials: L
authors.lastname: Vígh
authors.forename: Barna
authors.initials: B
authors.lastname: Peitl
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013004:Somatostatin / Q000097:blood; D013373:Substance P / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013373:Substance P; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide