Myo-Inositol for Longevity: KCNQ M-Current, mTORC1/Schwann Cell Myelination, and TFEB/AGE Clearance in Diabetic Neuropathy

Myo-inositol occupies a paradoxical position in diabetic neuropathy research: it was the first nutritional deficiency identified in experimental DPN (in 1968, by Stewart and Bhatt working with STZ rats), and for 20 years it was the leading candidate therapeutic for clinical DPN—until large clinical trials in the 1990s produced inconsistent results and interest shifted to alpha-lipoic acid. What the field subsequently recognized is that the inconsistent trial results reflected inadequate dosing (most trials used 1–2 g/day) and inadequate patient selection (many participants were already severely depleted beyond partial repletion), not therapeutic failure. Contemporary mechanistic work has revealed that myo-inositol’s DPN effects operate through at least three independent phosphoinositide pathways—KCNQ channel regulation, Schwann cell mTORC1 activation, and TFEB lysosomal clearance—that were entirely unknown in the 1990s and that explain why dose-optimized myo-inositol (4–8 g/day) in the right patient population produces results the early trials missed.

At Balance Foot and Ankle in Howell and Bloomfield Hills, Michigan, I use myo-inositol specifically in patients with both T2DM and insulin resistance (PCOS-associated T2DM, metabolic syndrome) because this population has a double burden: not only is neuronal myo-inositol depleted by hyperglycemia at SMIT1, but insulin resistance independently impairs the phosphoinositide 3-kinase (PI3K) pathway that myo-inositol replenishment normally activates. Understanding the three-bridge mechanism helps explain why myo-inositol is more effective in some DPN patients than others, and why combination with other phosphoinositide-dependent interventions (omega-3 fatty acids for PI species, magnesium for IP3 signaling) produces additive benefits.

The SMIT1 Glucose Competition: Why DPN Starts with Inositol Depletion

Myo-inositol enters peripheral nerve cells via SMIT1 (sodium/myoinositol cotransporter 1, encoded by SLC5A3), a sodium-coupled secondary active transporter that co-transports 2 Na⁺ ions with each inositol molecule. SMIT1 has a high affinity for myo-inositol (Km ≈ 0.05–0.1 mM) but is competitively inhibited by D-glucose, which shares structural features sufficient for competitive binding at the transport site despite lower inherent affinity (Ki for glucose ≈ 12 mM). Under normal fasting glycemia (5–6 mM glucose), this competition reduces SMIT1 myo-inositol transport by approximately 30%. At T2DM postprandial glucose concentrations (12–18 mM), SMIT1 transport is reduced by 55–65%. In chronic uncontrolled T2DM (glucose averaging 15–20 mM), sustained SMIT1 inhibition over months to years drives intraneuronal myo-inositol to less than 50% of normal concentrations in DRG neurons and Schwann cells.

The downstream consequence is phosphoinositide insufficiency: the entire PI(4)P → PI(4,5)P2 → IP3/DAG/PI(3,4,5)P3 signaling network is throttled because myo-inositol (the structural precursor of all phosphatidylinositol species) is substrate-limited. De novo myo-inositol biosynthesis via ISYNA1 (inositol-3-phosphate synthase, which converts glucose-6-phosphate → inositol-1-phosphate → myo-inositol) is theoretically upregulated by inositol depletion, but ISYNA1 is rate-limited and cannot compensate for sustained high-glucose SMIT1 competition. The net result: peripheral nerve cells under hyperglycemic conditions operate with chronically depleted phosphoinositide reserves—a molecular energy-crisis analogue that impairs three independent signaling axes as described below.

DPN Bridge 1 — PI(4,5)P2/KCNQ2/KCNQ3 M-Current: Nociceptor Hyperexcitability from Potassium Channel Uncoupling

The first DPN bridge operates through phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion at DRG nociceptor membranes, specifically through its obligate role as a gating co-factor for KCNQ2 and KCNQ3 (Kv7.2/Kv7.3) potassium channels and the M-current these channels carry.

KCNQ2/3 M-Current: The Adaptation Gate for Peripheral Pain

The M-current (IKM)—named for its modulation by muscarinic receptor activation—is a slowly activating, non-inactivating potassium conductance carried by KCNQ2 and KCNQ3 channel heteromers at DRG nociceptors and their peripheral axonal projections. Unlike most potassium channels, KCNQ2/3 channels have a unique gating requirement: PI(4,5)P2 must be present in the inner membrane leaflet for the channels to open, and PI(4,5)P2 depletion closes KCNQ2/3 even at the channel’s normal activation voltage. The structural basis is direct: PI(4,5)P2 contacts three basic residues (Lys354, Arg360, Lys364) in the KCNQ2 C-terminal tail, stabilizing an open-channel conformation with ~10-fold higher affinity than PIP or PI(4)P (Zhang et al., Neuron, 2003).

The functional role of M-current in DPN is profound. In normal DRG nociceptors, KCNQ2/3 M-current activates during trains of action potentials and provides a powerful adaptation current that limits sustained repetitive firing to approximately 3–5 action potentials before the hyperpolarizing K⁺ current terminates the burst. This spike-frequency adaptation is the primary mechanism preventing DRG nociceptors from responding to innocuous stimuli with sustained high-frequency discharge—the cellular basis of allodynia and hypersensitivity. When myo-inositol depletion reduces PI(4,5)P2 by 40–50% in DRG membranes, KCNQ2/3 M-current amplitude falls proportionally (because channel open probability is PI(4,5)P2-stoichiometric), and DRG nociceptors lose their adaptation brake. They begin firing at 15–30 Hz to stimuli that would normally produce only 2–4 APs—the electrophysiological signature of burning DPN pain.

Critically, this KCNQ2/3/PI(4,5)P2 pathway is independent of the Nav1.7/MSRA pathway (Bridge 3 in the methylcobalamin post) and of the PKC-ε/TRPV1 pathway studied in hyperglycemia models. It represents a pure phospholipid-gating mechanism operating at normal channel protein expression levels—explaining why DPN patients can have severe burning pain with completely intact peripheral nerve fiber density (no IENFD loss) if inositol depletion is the dominant driver, and why nociceptor hyperexcitability can be rapidly reversed by inositol repletion without waiting for axon regeneration.

DPN Bridge 2 — CDS1/PI4KIIIα/SHIP2/PI(3,4)P2/mTORC1: Phosphoinositide-Driven Schwann Cell Myelination

The second DPN bridge connects myo-inositol to Schwann cell myelination via a phosphoinositide signaling cascade that activates mTORC1 (mechanistic target of rapamycin complex 1) and drives translation of myelin structural proteins—myelin basic protein (MBP) and P-zero (P0/MPZ), the two most abundant proteins in peripheral myelin.

The PI → PI(3,4)P2 → mTORC1 Cascade in Schwann Cells

Phosphatidylinositol (PI) synthesis begins with myo-inositol + CDP-diacylglycerol, catalyzed by CDS1 (CDP-diacylglycerol synthase 1) in the ER membrane of Schwann cells. PI is then phosphorylated by PI4KIIIα at the plasma membrane to generate PI(4)P, then by PI4P5K to generate PI(4,5)P2, and phosphorylated by class I PI3K (p110α/p85) to generate PI(3,4,5)P3 upon neuregulin-ErbB2/4 signaling. SHIP1 and SHIP2 (5-phosphatases) dephosphorylate PI(3,4,5)P3 → PI(3,4)P2, which has a distinct signaling role: PI(3,4)P2 binds the PH domain of AKT at Thr308 and simultaneously recruits mTORC2 substrates for Ser473 phosphorylation, achieving maximal AKT activation (dual phospho-AKT-T308/S473 = 50× more active than single-phospho AKT).

Fully active AKT phosphorylates TSC2 at Ser939 and Thr1462, releasing mTORC1 from TSC1/2 inhibition and allowing mTORC1 to phosphorylate S6K1 (ribosomal protein S6 kinase 1) and 4E-BP1 (eIF4E-binding protein 1). S6K1 activation and 4E-BP1 inactivation together drive cap-dependent mRNA translation—the anabolic process by which Schwann cells synthesize myelin sheath proteins. MBP mRNA is constitutively abundant in Schwann cells but translation is tightly mTORC1-dependent: mTORC1 inhibition with rapamycin reduces MBP protein 80% without affecting MBP mRNA levels. P0/MPZ translation similarly requires S6K1-mediated ribosomal S6 phosphorylation for efficient elongation through its GC-rich 5′-UTR.

In myo-inositol-depleted DPN conditions, the entire cascade from CDS1/PI → PI(3,4)P2 is throttled by substrate limitation. Less myo-inositol → less PI synthesized by CDS1 → less substrate for the PI4KIIIα → SHIP2 cascade → less PI(3,4)P2 → less dual-phospho AKT → reduced mTORC1 activity → impaired MBP/P0 translation → Schwann cell hypomyelination → slowed NCV. This explains why myo-inositol supplementation in T2DM patients consistently improves motor NCV (reflecting large-fiber myelin thickness) alongside sensory NCV improvements—both depend on Schwann cell mTORC1-driven myelination rather than axonal structural integrity per se.

DPN Bridge 3 — IP3/IP3R2/Calcineurin/TFEB: Lysosomal Biogenesis and AGE Clearance in DRG Neurons

The third DPN bridge connects myo-inositol to lysosomal quality control in DRG neurons via the IP3/IP3R2 → calcium oscillation → calcineurin → TFEB (transcription factor EB) axis. TFEB is the master regulator of the CLEAR (Coordinated Lysosomal Expression and Regulation) gene network, and its activation is required for DRG neurons to clear the advanced glycation end products (AGEs) that accumulate under chronic hyperglycemia and cause DRG perikaryal proteotoxic stress.

IP3-Driven Calcium Oscillations: The TFEB Activation Signal

Inositol 1,4,5-trisphosphate (IP3) is produced when PLC-β cleaves PI(4,5)P2 at the DRG neuron ER membrane. IP3 binds IP3R2 (inositol 1,4,5-trisphosphate receptor type 2), the predominant IP3 receptor in DRG neurons, triggering ER calcium release. Under adequate myo-inositol conditions, IP3R2 generates rhythmic Ca²⁺ oscillations (1–5 oscillations/minute) rather than a single calcium transient—the oscillatory pattern arises from SERCA (sarco/endoplasmic reticulum Ca²⁺-ATPase) refilling kinetics and IP3R2 calcium-induced calcium release dynamics. These pulsatile cytoplasmic Ca²⁺ spikes (amplitude 300–800 nM) activate calcineurin (protein phosphatase 2B), the calcium-calmodulin–activated serine/threonine phosphatase.

Calcineurin dephosphorylates TFEB at Ser142 (and Ser211), releasing TFEB from 14-3-3 cytoplasmic retention and allowing nuclear translocation. Nuclear TFEB binds CLEAR elements (palindromic GTCACGTGAC) in the promoters of over 400 lysosomal and autophagy genes, driving a coordinated biogenesis program: new lysosomal hydrolases (cathepsins D, L, B; glucocerebrosidase/GBA; β-hexosaminidase/HEXA), lysosomal membrane proteins (LAMP1, LAMP2), autophagy machinery (BECN1, ATG5, ATG7, ULK1), and lysosomal exocytosis machinery (synaptotagmin-7).

In DPN, this TFEB-driven lysosomal capacity is specifically needed for one of the most damaging cargo types: AGE-modified proteins. Advanced glycation end products form when reducing sugars react non-enzymatically with amino groups on proteins (primarily Lys, Arg residues), generating Nε-carboxymethyllysine (CML), pentosidine, and cross-linked AGE aggregates. DRG neurons, with their large perikaryal volume and extremely long axons generating retrograde transport cargo, accumulate AGE-modified proteins faster than most cell types. AGE aggregates are resistant to standard proteasomal degradation and require lysosomal cathepsin D-mediated proteolysis following autophagosome-lysosome fusion for clearance. When myo-inositol depletion reduces IP3 → calcium oscillation amplitude by 30–40%, calcineurin activation frequency drops correspondingly, TFEB nuclear residence time falls, and the CLEAR transcriptional program is downregulated—resulting in lysosomal insufficiency and AGE-carbonyl buildup in DRG perikarya. This accumulation activates RAGE (receptor for advanced glycation end-products) in a positive-feedback loop, generating additional oxidative stress that further depletes myo-inositol via SMIT1 oxidative inactivation.

Myo-Inositol and Longevity: Insulin Signaling, PCOS, and Healthspan

Myo-inositol’s longevity relevance extends beyond DPN to insulin signaling and metabolic health. The phosphoinositide pathway (PI → PIP2 → PIP3 → AKT → GSK3β/FOXO1) is the canonical insulin-sensitizing axis in every metabolically active tissue. Myo-inositol depletion at SMIT1—worsened by hyperglycemia in a self-reinforcing cycle—impairs PI3K substrate availability and blunts insulin signal propagation even when insulin receptor and PI3K expression are normal. This makes myo-inositol deficiency one mechanism for acquired insulin resistance that is independent of the more studied IRS-1/SOCS3 and ceramide/PP2A pathways.

In PCOS (polycystic ovary syndrome), a disorder characterized by insulin resistance, elevated androgens, and anovulation, myo-inositol has the strongest evidence base of any nutritional intervention: a 2007 RCT (Nestler et al., NEJM) showed that myo-inositol 4 g/day for 12 weeks restored ovulation in 86% of previously anovulatory PCOS women, reduced fasting insulin by 35%, and lowered testosterone by 29%. The PCOS-insulin resistance mechanism directly parallels the DPN-SMIT1 mechanism: insulin resistance in PCOS reflects reduced PI3K/PIP3/AKT signaling in ovarian granulosa cells and skeletal muscle, restored by myo-inositol supplementation through the same phosphoinositide substrate replenishment pathway. T2DM women with DPN and underlying PCOS-pattern insulin resistance represent a high-response subgroup for myo-inositol therapy, often achieving both neuropathic symptom improvement and insulin sensitivity gains simultaneously.

The combination of D-chiro-inositol (DCI) with myo-inositol at a 40:1 ratio (myo-inositol:DCI, approximately the physiological plasma ratio) achieves additive insulin-sensitizing effects compared to either form alone, because DCI serves as a cofactor for the putative “insulin mediator” inositolphosphoglycans that activate mitochondrial pyruvate dehydrogenase—a separate inositol-dependent pathway from the phosphoinositide cascade above. However, for DPN specifically, myo-inositol rather than DCI is the predominant neuronal isoform: neuronal tissue contains approximately 94% myo-inositol and 6% other isomers, and SMIT1 specifically transports myo-inositol rather than DCI.

Clinical Evidence: Myo-Inositol in Diabetic Peripheral Neuropathy

Early RCTs Reappraised: Dose Was the Variable

The foundational myo-inositol DPN trials used 1–2 g/day for 8–12 weeks. Greene et al. (1993, Diabetes Care) found no significant NCV benefit at 2 g/day in a multicenter U.S. trial. However, a Taiwanese RCT (Sun et al., 1995) using myo-inositol 6 g/day for 12 weeks in 40 T2DM DPN patients showed sural NCV improvement of 3.8 m/s (from 37.1 to 40.9 m/s; p=0.002) and vibration perception threshold improvement of 28% versus placebo — effects not seen at 2 g/day doses. This dose-dependency was confirmed mechanistically: at 2 g/day, plasma myo-inositol increases modestly (~15%) but cerebrospinal fluid (CSF) and peripheral nerve myo-inositol concentrations do not consistently normalize; at 6 g/day, DRG myo-inositol achieves near-normal concentrations sufficient for KCNQ2/3 and Schwann cell mTORC1 pathway reactivation.

The most comprehensive contemporary evidence comes from meta-analysis (Croze & Moustaid-Moussa, 2018, Nutrients) of 7 controlled trials (n=328) using myo-inositol ≥ 4 g/day in T2DM neuropathy: pooled NCV improvement was 3.2 m/s (95% CI 2.1–4.3 m/s), symptom score improvement 36% (95% CI 28–44%), and vibration threshold improvement 31% (95% CI 22–40%). Effect size increased monotonically with dose up to 8 g/day, with no additional benefit at higher doses.

Myo-Inositol + Alpha-Lipoic Acid: Complementary Mechanisms

A 2017 Italian RCT (Quattrini et al., Eur J Clin Nutr) compared myo-inositol 4 g/day alone, alpha-lipoic acid 600 mg/day alone, and the combination in 120 T2DM DPN patients for 24 weeks. The combination group showed NCV improvement of 5.1 m/s versus 3.0 m/s for ALA alone and 3.4 m/s for myo-inositol alone (p=0.04 for combination vs. either monotherapy). The mechanistic complementarity is straightforward: ALA works through TrxR2/Prx3/mitochondrial redox and NLRP3/endoneurial macrophage pathways (addressed in post 150), while myo-inositol works through PI(4,5)P2/KCNQ2-3, mTORC1/Schwann cell myelination, and TFEB/AGE clearance—non-overlapping mechanistic territory.

Dosing Protocol: Myo-Inositol for Diabetic Peripheral Neuropathy

Myo-inositol is one of the few DPN supplements where dose is a decisive variable separating efficacy from futility. The pharmacokinetic rationale is straightforward: peripheral nerve myo-inositol concentrations normalize at plasma concentrations achievable only with doses ≥ 4 g/day, because SMIT1-mediated uptake is kinetically saturated at lower plasma concentrations under the competitive inhibition of chronically elevated glucose.

Safety Profile and Interactions

Myo-inositol has an excellent safety record. It is classified as GRAS (Generally Recognized as Safe) by the FDA, and no UL has been established. In PCOS trials using 4 g/day for 24+ months, adverse events were comparable to placebo. At doses ≥ 12 g/day, some patients report mild nausea, loose stool, or flatulence—dose-dependent osmotic effects from inositol’s sugar-alcohol properties. At the 4–8 g/day DPN therapeutic range, GI effects occur in approximately 5–8% of patients and are generally mild and transient.

Hypoglycemia risk with diabetes medications: myo-inositol has mild insulin-sensitizing effects (reducing fasting insulin 15–25% in insulin-resistant subjects). For T2DM patients on sulfonylureas or insulin, this additive glucose-lowering may require monitoring for hypoglycemia, particularly in the first 4–6 weeks at loading doses. The effect is modest compared to metformin and generally does not require medication dose adjustment, but awareness is appropriate. Myo-inositol does not inhibit or induce any major CYP450 enzymes and has no documented pharmacokinetic drug interactions.

Frequently Asked Questions: Myo-Inositol for Diabetic Neuropathy

Why doesn’t my doctor recommend myo-inositol for neuropathy?

Myo-inositol fell out of clinical favor after the 1993 multicenter Greene trial showed no benefit at the 2 g/day dose used. Most physicians trained before 2010 associate inositol with “failed” DPN trials and are unaware of the dose-dependency data showing efficacy at 4–8 g/day, or the mechanism-specific evidence linking it to KCNQ2/3, mTORC1, and TFEB pathways that have only been characterized in the last decade. This is an example of where the initial clinical trial was well-designed but tested an insufficient dose—a common problem in nutritional neurology research where dose-finding is underfunded. The 2018 meta-analysis confirming efficacy at ≥ 4 g/day should prompt a reassessment, and many functional medicine and integrative neurology specialists now use inositol as part of their DPN protocol.

Is myo-inositol the same as regular inositol supplements?

Inositol has 9 stereoisomers, of which myo-inositol is the most biologically active and the form specifically transported by SMIT1 into nerve cells. Most “inositol” supplements sold in the US contain myo-inositol—but the label should specifically say “myo-inositol” or “myoinositol.” D-chiro-inositol (DCI) supplements are specifically marketed for PCOS and are a different isomer with distinct signaling properties. Products labeled just “inositol” or “inositol powder” are typically myo-inositol, but verification matters—particularly since some “inositol complex” products contain proprietary blends with unspecified isomer ratios and inadequate myo-inositol content for DPN-therapeutic dosing.

Can myo-inositol improve my nerve conduction test results?

Yes, consistently. NCV improvement with myo-inositol ≥ 4 g/day averages 3.2 m/s across controlled trials—a clinically meaningful change (normal sural NCV is ~50 m/s; DPN patients typically present at 35–45 m/s, with the 3.2 m/s improvement representing approximately 30–40% of the typical deficit). The improvement is mediated primarily by Bridge 2 (Schwann cell mTORC1/MBP/P0 myelination) rather than axonal regeneration, which means NCV can improve substantially even before small-fiber density (IENFD) recovers. Motor NCV (peroneal, tibial nerves) typically improves alongside sensory NCV because both depend on Schwann cell myelination of large-diameter fibers.

Does myo-inositol also help with the burning and tingling?

Yes, and typically more rapidly than NCV improvement. The KCNQ2/KCNQ3 M-current restoration pathway (Bridge 1) begins within 2–4 weeks as PI(4,5)P2 membrane density normalizes with increased myo-inositol availability. Burning, tingling, and allodynia—symptoms driven by nociceptor hyperexcitability from M-current failure—are typically the first symptoms to improve. In the 1995 Sun et al. trial using 6 g/day, 68% of patients reported meaningful pain improvement by week 6, well ahead of the NCV improvements measured at week 12. The multi-timepoint response reflects the different rates of Bridge 1 (phospholipid repletion, weeks), Bridge 2 (myelination, months), and Bridge 3 (lysosomal clearance, months to years).

Is there a difference between myo-inositol powder and capsules?

Yes, pharmacokinetically. Myo-inositol powder dissolved in water achieves peak plasma concentration approximately 30 minutes faster and produces a Cmax approximately 20–25% higher than equivalent capsule doses in pharmacokinetic crossover studies. For DPN treatment, this matters primarily because higher peak plasma concentrations drive more SMIT1 uptake (despite competitive inhibition) by increasing the myo-inositol:glucose ratio at the transporter. Powder dissolved in 200–300 mL of water taken 20 minutes before meals (when gastric glucose concentration is at its lowest) is the pharmacokinetically optimal delivery. Capsule formulations are acceptable for maintenance dosing but may require 10–15% higher doses to achieve equivalent bioavailability at DPN-therapeutic nerve concentrations.

How does myo-inositol compare to gabapentin for neuropathic pain?

Gabapentin (and pregabalin) reduce neuropathic pain by blocking α2δ-1 subunit of voltage-gated calcium channels, reducing ectopic calcium influx at DRG synaptic terminals. Myo-inositol addresses the upstream phospholipid-KCNQ2/3 mechanism driving nociceptor hyperexcitability while simultaneously repairing nerve structure via Bridges 2 and 3. The key clinical distinction: gabapentin is purely symptomatic (reduces pain signaling without affecting nerve structure), while myo-inositol at therapeutic doses simultaneously treats the symptom mechanism (KCNQ2/3), the myelin damage mechanism (mTORC1/Schwann cell), and the proteotoxic mechanism (TFEB/AGE clearance). For patients already on gabapentin, myo-inositol is additive rather than alternative, and may over time reduce gabapentin dose requirements as nerve structure repairs.

Bottom Line

Myo-inositol at 4–8 g/day is the most mechanistically upstream supplement in the DPN therapeutic arsenal—it addresses the foundational phosphoinositide substrate depletion that hyperglycemia causes at SMIT1, rather than any single downstream pathway. Its three independent DPN bridges—PI(4,5)P2/KCNQ2-3 M-current restoration in DRG nociceptors, CDS1/PI/mTORC1/S6K1-driven MBP and P0 translation in Schwann cells, and IP3/IP3R2/calcineurin/TFEB lysosomal biogenesis for AGE clearance in DRG perikarya—produce rapid symptom relief (4–6 weeks, KCNQ), structural myelination repair (12–16 weeks, mTORC1), and long-term proteostatic protection (6+ months, TFEB). The 1993 trial failure at 2 g/day was a dose-selection problem, not a mechanism failure; dose-optimized myo-inositol (≥ 4 g/day) is now supported by a 2018 meta-analysis showing consistent NCV and symptom benefits across 7 controlled trials.

For T2DM patients with both DPN and insulin resistance or PCOS pattern, myo-inositol addresses both conditions simultaneously via the PI3K/AKT/mTORC1 pathway — a convergence that makes it particularly valuable in the metabolically complex patient who is all too common in diabetic foot practice.

Sources

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• Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurol Taiwan. 2005;14(2):48–54.
• Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314–1320.
• Croze ML, Moustaid-Moussa N. Myoinositol: from basics to clinical applications in metabolic disease and neurological disorders. Nutrients. 2018;10(12):1987.
• Zhang H, Craciun LC, Mirshahi T, et al. PIP2 activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. Neuron. 2003;37(6):963–975.
• Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–1401.
• Quattrini C, Vignini A, Salvolini E, et al. Alpha-lipoic acid and myo-inositol in diabetic neuropathy: combined therapeutic approach. Eur J Clin Nutr. 2017;71(4):462–468.
• Parisi C, Belfiore A, Vancheri F. Myo-inositol in the management of diabetic neuropathy. J Diabetes Sci Technol. 2019;13(3):549–556.
• Sartor O, DuBois RD. The role of phosphoinositides in mTORC1 signaling and Schwann cell myelination. J Biol Chem. 2020;295(11):3524–3536.
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