Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.

Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.

Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance.

Alzheimer's disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer's disease. The pathogenesis of Alzheimer's disease is mainly mediated by the phosphorylation and aggregation of tau protein. Among the multiple causes of tau hyperphosphorylation, brain insulin resistance has generated much attention, and inositols as insulin sensitizers, are currently considered candidates for drug development.

Surveillance for gastrointestinal, subcutaneous, and ectoparasites of invasive North American raccoons (Procyon lotor) in central Spain.

The American raccoon (Procyon lotor) is an invasive meso-carnivore which has been introduced and established in many European countries. Although the presence of the raccoon in the Iberian Peninsula was confirmed around 20 years ago, there are few data on pathogens of these animals in this region. For this work, 72 American raccoons from two subpopulations in the central region of the Iberian Peninsula were examined for selected parasites.

Pharmacokinetics and Endocrine Effects of an Oral Dose of D-Pinitol in Human Fasting Healthy Volunteers.

The present study characterizes the oral pharmacokinetics of D-Pinitol, a natural insulin mimetic inositol, in human healthy volunteers (14 males and 11 females). D-Pinitol absorption was studied in (a) subjects receiving a single oral dose of 15 mg/kg ( = 10), or (b) 5 mg/kg pure D-Pinitol ( = 6), and (c) subjects receiving D-Pinitol as part of carbohydrate-containing carob pods-derived syrup with a 3.2% D-Pinitol (Dose of 1600 mg/subject, = 9).

Endocrine and Metabolic Impact of Oral Ingestion of a Carob-Pod-Derived Natural-Syrup-Containing D-Pinitol: Potential Use as a Novel Sweetener in Diabetes.

The widespread use of added sugars or non-nutritive sweeteners in processed foods is a challenge for addressing the therapeutics of obesity and diabetes. Both types of sweeteners generate health problems, and both are being blamed for multiple complications associated with these prevalent diseases. As an example, fructose is proven to contribute to obesity and liver steatosis, while non-nutritive sweeteners generate gut dysbiosis that complicates the metabolic control exerted by the liver.

d-Pinitol promotes tau dephosphorylation through a cyclin-dependent kinase 5 regulation mechanism: A new potential approach for tauopathies?

Background And Purpose: Recent evidence links brain insulin resistance with neurodegenerative diseases, where hyperphosphorylated tau protein contributes to neuronal cell death. In the present study, we aimed to evaluate if d-pinitol inositol, which acts as an insulin sensitizer, affects the phosphorylation status of tau protein.

Experimental Approach: We studied the pharmacological effect of d-pinitol on insulin signalling and tau phosphorylation in the hippocampus of Wistar and Zucker rats.

Dietary administration of D-chiro-inositol attenuates sex-specific metabolic imbalances in the 5xFAD mouse model of Alzheimer's disease.

Increasing evidence shows that hypothalamic dysfunction, insulin resistance, and weight loss precede and progress along with the cognitive decline in sporadic Alzheimer's Disease (AD) with sex differences. This study aimed to determine the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance associated with polycystic ovary, on the occurrence of metabolic disorders in the transgenic 5xFAD mouse model of AD (FAD: Family Alzheimer's Disease). DCI was administered from 6 to 10 months of age to male and female 5xFAD mice and control (non-Tg) littermates.

Activation of PI3K/Akt Signaling Pathway in Rat Hypothalamus Induced by an Acute Oral Administration of D-Pinitol.

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN.

A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse.

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer's disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus.

D-Chiro-Inositol Treatment Affects Oocyte and Embryo Quality and Improves Glucose Intolerance in Both Aged Mice and Mouse Models of Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is the main cause of female infertility. It is a multifactorial disorder with varying clinical manifestations including metabolic/endocrine abnormalities, hyperandrogenism, and ovarian cysts, among other conditions. D--inositol (DCI) is the main treatment available for PCOS in humans.

The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases.

Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties.

D-Pinitol from Is an Orally Active Natural Inositol That Reduces Pancreas Insulin Secretion and Increases Circulating Ghrelin Levels in Wistar Rats.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and its effects on (a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), (b) insulin signaling in the liver and (c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity.