Insulin prevents aberrant mitochondrial phenotype in sensory neurons of type 1 diabetic rats.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro laboratory study
PubMed 28803751 · doi:10.1016/j.expneurol.2017.08.005
What was done
Cultured dorsal root ganglion (DRG) sensory neurons from adult control and streptozotocin (STZ)-induced type 1 diabetic rats were treated with or without insulin (10 nM) to measure Akt/P70S6K phosphorylation, neurite outgrowth, and mitochondrial respiration. In vivo, control and STZ-diabetic rats were maintained for 5 months with or without trace insulin supplementation, and evaluated for DRG respiratory chain expression, cytochrome c oxidase activity, dermal nerve density, and hind paw thermal sensitivity.
What was found
In vitro, 10 nM insulin significantly (P < 0.05) increased phosphorylation of Akt and P70S6K by 4-fold and neurite outgrowth by 2-fold in control DRG cultures, and increased spare respiratory capacity by up to 3-fold (P < 0.05) in cultures from control and diabetic rats. In vivo, 5 months of trace insulin supplementation corrected suppressed DRG mitochondrial respiratory chain protein expression and cytochrome c oxidase activity, improved hind paw thermal sensitivity, and increased dermal nerve density compared to untreated diabetic rats, without altering blood glucose levels.
Why it matters
These findings suggest that direct neurotrophic insulin signaling maintains sensory neuron mitochondrial function and protects against peripheral neuropathy markers independently of glycemic control.
Limits
The study is restricted to rodent models and cell culture preparations, which may not fully replicate human diabetic neuropathy. Sample sizes (n) for animals and cell preparations are not reported in the abstract, and non-glycemic mechanisms in humans remain unverified.
Cited by
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