title: Activation of the insulin-signaling pathway in sciatic nerve and hippocampus of type 1 diabetic rats.
abstract: Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer's disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the peripheral nervous system (PNS) and central nervous system (CNS) of insulin-dependent type 1 diabetic rats. Fresh sciatic nerve and hippocampus from control and diabetic rats were incubated with varied ex vivo concentrations of insulin and phosphorylation levels of insulin receptor and glycogen synthase kinase-3 (GSK3β) were assessed by Western blot analysis. Both the sciatic nerve and hippocampus from type 1 diabetic rats were highly responsive to exogenous insulin with a significantly increased phosphorylation of insulin receptor and GSK3 compared to tissues from control rats. Further, sustained in vivo insulin delivery, not sufficient to restore normal blood glucose, normalized the activation of both insulin receptor and GSK3 in both PNS and CNS tissues. These results suggest that the insulin-signaling pathway is responsive to exogenous insulin in the nervous system of insulin-deficient type 1 diabetic rats and that constant insulin delivery restore normal nerve function and may protect PNS and CNS from damage.
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: King
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Anderson
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: E
authors.initials: E
authors.lastname: Law
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cundiff
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Mixcoatl-Zecuatl
authors.affiliation: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: cjolivalt@ucsd.edu.
authors.forename: C G
authors.initials: CG
authors.lastname: Jolivalt
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: GSK3; diabetes; hippocampus; insulin; insulin receptor; sciatic nerve