19 Harley St, London, W1G 9QJ, UK

Hyperinsulinemia induces insulin resistance in dorsal root ganglion neurons

Insulin resistance (IR) is the major feature of metabolic syndrome, including type 2 diabetes. IR studies are mainly focused on peripheral tissues, such as muscle and liver. There is, however, little knowledge about IR in neurons. In this study, we examined whether neurons develop IR in response to hyperinsulinemia. We first examined insulin signaling using adult dorsal root ganglion neurons as a model system. Acute insulin treatment resulted in time- and concentration-dependent activation of the signaling cascade, including phosphorylation of the insulin receptor, Akt, p70S6K, and glycogen synthase kinase-3beta. To mimic hyperinsulinemia, cells were pretreated with 20 nM insulin for 24 h and then stimulated with 20 nM insulin for 15 min. Chronic insulin treatment resulted in increased basal Akt phosphorylation. More importantly, acute insulin stimulation after chronic insulin treatment resulted in blunted phosphorylation of Akt, p70S6K, and glycogen synthase kinase-3beta. Interestingly, when the cells were treated with phosphatidylinositol 3-kinase pathway inhibitor, but not MAPK pathway inhibitor, chronic insulin treatment did not block acute insulin treatment-induced Akt phosphorylation. Insulin-induced Akt phosphorylation was lower in dorsal root ganglion neurons from BKS-db/db compared with control BKS-db+ mice. This effect was age dependent. Our results suggest that hyperinsulinemia cause IR by disrupting the Akt-mediated pathway. We also demonstrate that hyperinsulinemia increases the mitochondrial fission protein dynamin-related protein 1. Our results suggest a new theory for the etiology of diabetic neuropathy, i.e. that, similar to insulin dependent tissues, neurons develop IR and, in turn, cannot respond to the neurotrophic properties of insulin, resulting in neuronal injury and the development of neuropathy

Keywords : Adult,Animals,Diabetic Neuropathies,etiology,Extracellular Signal-Regulated MAP Kinases,Ganglia,Spinal,Hyperinsulinism,injuries,Insulin Resistance,Liver,metabolism,Mice,Mice,Inbred C57BL,Neurons,Phosphorylation,Proto-Oncogene Proteins c-akt,Rats,Rats,Sprague-Dawley,Syndrome,Time,, Induces,Insulin,Resistance,Dorsal, physiotherapist london

Date of Publication : 2011 Oct

Authors : Kim B;McLean LL;Philip SS;Feldman EL;

Organisation : University of Michigan, Department of Neurology, 109 Zina Pitcher Place, 5371 BSRB, Ann Arbor, Michigan 48109-2200, USA. bhumsoo@umich.edu

Journal of Publication : Endocrinology

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21810948

The London Spine Unit : Harley Street UK. Specialists in Cutting Edge Technologies for Spinal Surgery

Make an Appointment 

Trustpilot Reviews
Doctify Reviews
Top Doctor Reviews

Hyperinsulinemia Induces Insulin Resistance in Dorsal Root Ganglion Neurons | Piriformis syndrome patient uk

What our patients say ...

Consultant Spine Surgeon
Consultant Spine Surgeon
Consultant Spine Surgeon

This surgical technique consists of a percutaneous approach for the treatment of small to medium size hernias of the intervertebral disc by laser energy. The main objective is to reduce the intradiscal pressure in the nucleus pulposus

Laser Disc Surgery can be performed under local anaesthetic as a day case at our centre on the prestigious Harley Street.
What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

treatment of all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

If you have any emergency Doctor’s need, simply call our 24 hour emergency

Your personal case manager will ensure that you receive the best possible care.

Call Now 

+44 844 589 2020
+44 203 973 8810