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Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

ABSTRACT: Insulin resistance, induced by high fructose consumption, affects cognitive function negatively. Nifedipine may be suggested for neurological disorders. This study aimed to assess the effect of nifedipine with either a normal diet (ND) or a ketogenic diet (KD) in cognitive dysfunction. Male Wistar rats received 10% fructose in drinking water for 8 weeks to induce insulin resistance. Rats received nifedipine (5.2 mg/kg/day; p.o.) later with ND or KD for an additional five weeks. One and two-way ANOVAs were used in analyzing the data. Reversion to the ND improved insulin resistance and lipid profile, besides brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 beta (GSK3β), and insulin-degrading enzyme (IDE) levels. Rats fed KD alone and those that received nifedipine with KD did not show similar improvement in the previously mentioned parameters as the ND group. However, nifedipine-ND rats showed improvement in cognitive behavior and insulin resistance. Treatment with nifedipine-KD ameliorated GSK3β, amyloid β (Aβ), and tau protein levels. As the nifedipine-KD combination succeeded in diminishing the accumulated Aβ and tau protein, KD may be used for a while due to its side effects, then nifedipine treatment could be continued with an ND. This conclusion is based on the finding that this combination mitigated insulin resistance with the associated improved behavior.

SUBMITTER: Abdel-Kareem NM

PROVIDER: S-EPMC11359371 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

Abdel-Kareem Nancy M NM Elshazly Shimaa M SM Abd El Fattah May A MA Aldahish Afaf A AA Zaitone Sawsan A SA Ali Sahar K SK Abd El-Haleim Enas A EA

Pharmaceuticals (Basel, Switzerland) 20240810 8

Insulin resistance, induced by high fructose consumption, affects cognitive function negatively. Nifedipine may be suggested for neurological disorders. This study aimed to assess the effect of nifedipine with either a normal diet (ND) or a ketogenic diet (KD) in cognitive dysfunction. Male Wistar rats received 10% fructose in drinking water for 8 weeks to induce insulin resistance. Rats received nifedipine (5.2 mg/kg/day; p.o.) later with ND or KD for an additional five weeks. One and two-way A ...[more]

PMID: 39204160

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Project description:BackgroundMembers of the aging population who undergo surgery are at risk of postoperative cognitive dysfunction (POCD). Exploring an effective and reliable early predictor of POCD is essential to the identification of high-risk patients and to making prospective decisions. The purpose of this study was to examine whether preoperative insulin resistance is an independent predictor of POCD.MethodsA total of 124 patients aged 60 years and older and who were scheduled for gastrointestinal surgery were enrolled in a prospective observational clinical study. All participants completed a battery of neuropsychological tests before surgery and 7 days later. POCD was defined as a decline of at least 1.5 SD on two or more of neuropsychological tests. Plasma concentration of the tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and S-100β protein were measured. The status of insulin resistance was assessed by Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The relationship between HOMA-IR and POCD was assessed by Multivariable logistic regression models and the receiver operating characteristic (ROC) curve.ResultsFifty one patients (41.1%) were diagnosed with POCD at 7 days after surgery. Preoperative HOMA-IR values of the POCD group were significantly higher than the non-POCD group. Furthermore, CRP and TNF-α levels of the POCD group were significantly higher at each postoperative time point (P < 0.05). The preoperative HOMA-IR value was an independent predictor of POCD (adjusted OR 1.88, 95% CI, 1.18-2.99) even after adjust for confounding variables, and when dichotomized, individuals above the HOMA-IR threshold (HOMA-IR > 2.6) had a three-times higher risk of POCD (OR 3.26; 95% CI, 1.07-9.91) compared to individuals below the threshold. The areas under the ROC curve of HOMA-IR was 0.804 (95% CI, 0.725-0.883; P < 0.001). The optimal cut-off value was found to be 0.583, with a sensitivity of 84.3% and specificity of 74%. The HOMA-IR value was positively associated with the TNF-α concentration at baseline (R 2 = 0.43, P < 0.01) and 1 day after surgery (R 2 = 0.3861, P < 0.01).ConclusionPreoperative insulin resistance is an effective predictor for the occurrence of POCD. Targeted prevention and treatment strategies of insulin resistance may be effective interventions of patients at risk for POCD.

Dataset Information

Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

Publications

Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

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