Chronic treatment with d-chiro-inositol prevents autonomic and somatic neuropathy in STZ-induced diabetic mice

Farias, Vanessa Ximenes; Macedo, Flávio Henrique Pequeno de; Oquendo, MA; Tomé, Adriana R.; Báo, Sônia Nair; Cintra, D.O.S.; Santos, Cláudia Ferreira; Albuquerque, André; Heimark, Douglas; Larner, Joseph; Fonteles, M. C.; Leal‐Cardoso, J. H.; Nascimento, Nilberto R.F.

doi:10.1111/j.1463-1326.2010.01344.x

Cited by 23 publications

(22 citation statements)

References 48 publications

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“…The finding that chiro-inositols activate insulin signaling in CNS neurons is in harmony with results established previously in peripheral tissues, which demonstrated increased plasma glucose utilization in rats and rhesus monkeys after chiro-inositol administration (42,62). Insulin mimetic effects are consistent with the ability of DCI to protect against autonomic and somatic neuropathy in diabetic mice (44). Our results extend this protection against neuropathy to CNS neurons in a manner that is germane to Alzheimer's pathogenesis.…”

Section: Discussionsupporting

confidence: 91%

Protection against the synaptic targeting and toxicity of Alzheimer's‐associated Aβ oligomers by insulin mimetic chiro‐inositols

et al. 2012

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Alzheimer's disease (AD) is a progressive dementia that correlates highly with synapse loss. This loss appears due to the synaptic accumulation of toxic Aβ oligomers (ADDLs), which damages synapse structure and function. Although it has been reported that oligomer binding and toxicity can be prevented by stimulation of neuronal insulin signaling with PPARγ agonists, these agonists have problematic side effects. We therefore investigated the therapeutic potential of chiro-inositols, insulin-sensitizing compounds safe for human consumption. Chiro-inositols have been studied extensively for treatment of diseases associated with peripheral insulin resistance, but their insulin mimetic function in memory-relevant central nervous system (CNS) cells is unknown. Here we demonstrate that mature cultures of hippocampal neurons respond to d-chiro-inositol (DCI), pinitol (3-O-methyl DCI), and the inositol glycan INS-2 (pinitol β-1-4 galactosamine) with increased phosphorylation in key upstream components in the insulin-signaling pathway (insulin receptor, insulin receptor substrate-1, and Akt). Consistent with insulin stimulation, DCI treatment promotes rapid withdrawal of dendritic insulin receptors. With respect to neuroprotection, DCI greatly enhances the ability of insulin to prevent ADDL-induced synapse damage (EC(50) of 90 nM). The mechanism comprises inhibition of oligomer binding at synapses and requires insulin/IGF signaling. DCI showed no effects on Aβ oligomerization. We propose that inositol glycans and DCI, a compound already established as safe for human consumption, have potential as AD therapeutics by protecting CNS synapses against Aβ oligomers through their insulin mimetic activity.

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Section: Discussionsupporting

confidence: 91%

Protection against the synaptic targeting and toxicity of Alzheimer's‐associated Aβ oligomers by insulin mimetic chiro‐inositols

et al. 2012

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“…Diabetic db/db mice, diabetic Rhesus monkeys and T2D patients showed a linear correlation between decreased urinary DCI excretion and the degree of insulin resistance . Previously, it was reported that DCI decreases the level of oxidative stress in endothelial cells, and DCI seems to prevent the inflammatory neuronal damages observed in rats treated with streptozotocin …”

Section: Introductionmentioning

confidence: 90%

C ucurbita ficifolia Bouché (Cucurbitaceae) and D-chiro-inositol modulate the redox state and inflammation in 3T3-L1 adipocytes

Fortis-Barrera

Alarcón-Aguilar

Banderas-Dorantes

et al. 2013

Journal of Pharmacy and Pharmacology

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“…For induction of diabetes we used a previously described methodology [11]. The mice were subjected to fasting for 6 hours and then anesthetized by thiopental (40mg/kg/2.5% IP) and kept in a prone position for an intraperitoneal (IP) injection of streptozotocin (solution 70mg/kg - STZ) dissolved in citrate buffer solution (pH 4.5).…”

Section: 0 Materials and Methodsmentioning

confidence: 99%

Low-level laser therapy (904nm) can increase collagen and reduce oxidative and nitrosative stress in diabetic wounded mouse skin

Tatmatsu-Rocha

Ferraresi

Hamblin

et al. 2016

Journal of Photochemistry and Photobiology B: Biology

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Background and Objective Over the last decade we have seen an increased interest in the use of Low-Level Laser Therapy (LLLT) in diseases that involve increased oxidative stress. It is well established that hyperglycemia in diabetes elicits a rise in reactive oxygen species (ROS) production but the effect of LLLT remains unclear. This study aimed to investigate whether LLLT was able to improve oxidative/nitrosative stress parameters in the wound healing process in diabetic mice. Study Design/Materials and Methods Twenty male mice were divided into four groups: non-irradiated control (NIC), irradiated control (IC), non-irradiated and diabetic (NID), irradiated and diabetic (ID). Diabetes was induced by administration of streptozotocin. Wounds were created 120 days after the induction of diabetes in groups IC and ID and these groups were irradiated daily for 5 days (superpulsed 904 nm laser, average power 40 mW, 60 sec). All animals were sacrificed 1 day after the last irradiation and histology, collagen amount, catalase activity, nitrite and thiobarbituric acid reactive substances (TBARS) were measured. Results Histology showed that collagen fibers were more organized in IC and ID when compared to NID group, and significant differences in collagen content were found in group ID versus NID. Catalase activity was higher in IC group compared to other groups (p < 0.001). TBARS levels were higher in IC versus NIC, but were lower in ID versus NID (p < 0.001). Nitrite was lower in both irradiated groups versus the respective non-irradiated groups (p < 0.001). Conclusions Delayed wound healing in diabetes is still a challenge in clinical practice with high social costs. The increased production of collagen and decreased oxidative and nitrosative stress suggests that LLLT may be a viable therapeutic alternative in diabetic wound healing.

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Chronic treatment with d-chiro-inositol prevents autonomic and somatic neuropathy in STZ-induced diabetic mice

Abstract: DCI has a neuroprotective action in both autonomic and somatic nerves in STZ-induced DN.

Cited by 23 publications

References 48 publications

Protection against the synaptic targeting and toxicity of Alzheimer's‐associated Aβ oligomers by insulin mimetic chiro‐inositols

Protection against the synaptic targeting and toxicity of Alzheimer's‐associated Aβ oligomers by insulin mimetic chiro‐inositols

C ucurbita ficifolia Bouché (Cucurbitaceae) and D-chiro-inositol modulate the redox state and inflammation in 3T3-L1 adipocytes

Low-level laser therapy (904nm) can increase collagen and reduce oxidative and nitrosative stress in diabetic wounded mouse skin

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