Insulin prevents depolarization of the mitochondrial inner membrane in sensory neurons of type 1 diabetic rats in the presence of sustained hyperglycemia.
Mitochondrial dysfunction has been proposed as a mediator of neurodegeneration in diabetes complications. The aim of this study was to determine whether deficits in insulin-dependent neurotrophic support contributed to depolarization of the mitochondrial membrane in sensory neurons of streptozocin (STZ)-induced diabetic rats. Whole cell fluorescent video imaging using rhodamine 123 (R123) was used to monitor mitochondrial inner membrane potential (deltapsi(m)). Treatment of cultured dorsal root ganglia (DRG) sensory neurons from normal adult rats for up to 1 day with 50 mmol/l glucose had no effect; however, 1.0 nmol/l insulin increased deltapsi(m) by 100% (P < 0.05). To determine the role of insulin in vivo, STZ-induced diabetic animals were treated with background insulin and the deltapsi(m) of DRG sensory neurons was analyzed. Insulin therapy in STZ-induced diabetic rats had no effect on raised glycated hemoglobin or sciatic nerve polyol levels, confirming that hyperglycemia was unaffected. However, insulin treatment significantly normalized diabetes-induced deficits in sensory and motor nerve conduction velocity (P < 0.05). In acutely isolated DRG sensory neurons from insulin-treated STZ animals, the diabetes-related depolarization of the deltapsi(m) was corrected (P < 0.05). The results demonstrate that loss of insulin-dependent neurotrophic support may contribute to mitochondrial membrane depolarization in sensory neurons in diabetic neuropathy.
Huang
Tze-Jen
TJ
School of Biological Sciences, University of Manchester, Manchester, UK.
Price
Sally A
SA
Chilton
Lucy
L
Calcutt
Nigel A
NA
Tomlinson
David R
DR
Verkhratsky
Alex
A
Fernyhough
Paul
P
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control; D005727:Ganglia, Spinal / Q000166:cytology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018715:Microscopy, Video; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011108:Polymers / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000502:physiology
D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; C024617:polyol; D011972:Receptor, Insulin; D005947:Glucose