ArticleMolecular metabolism2019
Insulin-like growth factor-1 activates AMPK to augment mitochondrial function and correct neuronal metabolism in sensory neurons in type 1 diabetes.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 70 citations in OpenAlex.
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- Association between low-grade inflammation and distal sensorimotor polyneuropathy in type 2 diabetes: a cross-sectional study.BMC neurology · 2025Article
- Muscarinic Receptor Antagonism and TRPM3 Activation as Stimulators of Mitochondrial Function and Axonal Repair in Diabetic Sensorimotor Polyneuropathy.International journal of molecular sciences · 2025Review
- IGF1 Signaling Regulates Neuropeptide Expression in Hypothalamic Neurons Under Physiological and Pathological Conditions.Endocrinology · 2025Article
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- Impaired Fibroblast Growth Factor 21 (FGF21) Associated with Visceral Adiposity Leads to Insulin Resistance: The Core Defect in Diabetes Mellitus.Current diabetes reviews · 2025Review
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
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- Diminished levels of insulin-like growth factor-1 may be a risk factor for peripheral neuropathy in type 2 diabetes patients.Journal of diabetes investigation · 2024Article
- Cytokine-Supplemented Maturation Medium Enhances Cytoplasmic and Nuclear Maturation in Bovine Oocytes.Animals : an open access journal from MDPI · 2024Article
- Insulin-like growth factor-1 reduces cardiac autosis through decreasing AMPK/FOXO1 signaling and NaArchives of medical science : AMS · 2024Article
- Increased IGFBP2 Levels by Placenta-Derived Mesenchymal Stem Cells Enhance Glucose Metabolism in a TAA-Injured Rat Model via AMPK Signaling Pathway.International journal of molecular sciences · 2023Article
- The Dynamics of Nerve Degeneration and Regeneration in a Healthy Milieu and in Diabetes.International journal of molecular sciences · 2023Review
- Neuroprotective Effects of Probiotic Lactobacillus reuteri GMNL-263 in the Hippocampus of Streptozotocin-Induced Diabetic Rats.Probiotics and antimicrobial proteins · 2023Article
- New perspectives in diabetic neuropathy.Neuron · 2023Review
- Article
- Rodent Models of Diabetic Retinopathy as a Useful Research Tool to Study Neurovascular Cross-Talk.Biology · 2023Review
- Identification of the molecular mechanism of insulin-like growth factor-1 (IGF-1): a promising therapeutic target for neurodegenerative diseases associated with metabolic syndrome.Cell & bioscience · 2023Review
- Role of insulin-like growth factor 1 (IGF1) in the regulation of mitochondrial bioenergetics in zebrafish oocytes: lessons fromFrontiers in cell and developmental biology · 2023Article
- Advantages of omics approaches for elucidating metabolic changes in diabetic peripheral neuropathy.Frontiers in endocrinology · 2023Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveDiabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) of animal models of type 1 and type 2 diabetes. We hypothesized that sub-optimal insulin-like growth factor 1 (IGF-1) signaling in diabetes drives loss of AMPK activity and mitochondrial function, both contributing to development of DSPN.
methodsAge-matched control Sprague-Dawley rats and streptozotocin (STZ)-induced type 1 diabetic rats with/without IGF-1 therapy were used for in vivo studies. For in vitro studies, DRG neurons from control and STZ-diabetic rats were cultured and treated with/without IGF-1 in the presence or absence of inhibitors or siRNAs.
resultsDysregulation of mRNAs for IGF-1, AMPKα2, ATP5a1 (subunit of ATPase), and PGC-1β occurred in DRG of diabetic vs. control rats. IGF-1 up-regulated mRNA levels of these genes in cultured DRGs from control or diabetic rats. IGF-1 treatment of DRG cultures significantly (P < 0.05) increased phosphorylation of Akt, P70S6K, AMPK and acetyl-CoA carboxylase (ACC). Mitochondrial gene expression and oxygen consumption rate (spare respiratory capacity), ATP production, mtDNA/nDNA ratio and neurite outgrowth were augmented (P < 0.05). AMPK inhibitor, Compound C, or AMPKα1-specific siRNA suppressed IGF-1 elevation of mitochondrial function, mtDNA and neurite outgrowth. Diabetic rats treated with IGF-1 exhibited reversal of thermal hypoalgesia and, in a separate study, reversed the deficit in corneal nerve profiles. In diabetic rats, IGF-1 elevated the levels of AMPK and P70S6K phosphorylation, raised Complex IV-MTCO1 and Complex V-ATP5a protein expression, and restored the enzyme activities of Complex IV and I in the DRG. IGF-1 prevented TCA metabolite build-up in nerve.
conclusionsIn DRG neuron cultures IGF-1 signals via AMPK to elevate mitochondrial function and drive axonal outgrowth. We propose that this signaling axis mediates IGF-1-dependent protection from distal dying-back of fibers in diabetic neuropathy.
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