Dataset Information

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

ABSTRACT:

Background

Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes.

Aims

To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats.

Methods

Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry.

Results

Our data showed a pronounced decrease in the phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type 1 and type 2 diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I (Ser 603) and GluR1 (Ser 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP1? and PP2A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up-regulated in type 2 diabetic rats.

Conclusions

The disturbance of CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.

SUBMITTER: Liao MH

PROVIDER: S-EPMC6493428 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

Liao Mei-Hua MH Xiang Ying-Chun YC Huang Ji-Yun JY Tao Rong-Rong RR Tian Yun Y Ye Wei-Feng WF Zhang Gen-Sheng GS Lu Ying-Mei YM Ahmed Muhammad M MM Liu Zhi-Rong ZR Fukunaga Kohji K Han Feng F

CNS neuroscience & therapeutics 20130314 5

<h4>Background</h4>Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes.<h4>Aims</h4>To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats.<h4>Methods</h4>Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting ...[more]

PMID: 23490331

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Project description:BackgroundShort sleep duration and poor sleep quality are important risk factors for atherosclerosis. The use of smart bracelets that measure sleep parameters, such as sleep stage, can help determine the effect of sleep quality on lower-extremity atherosclerosis in patients with type 2 diabetes.ObjectiveTo investigate the correlation between sleep disorders and lower-extremity atherosclerosis in patients with type 2 diabetes.MethodsAfter admission, all patients were treated with lower-extremity arterial ultrasound and graded as having diabetic lower-extremity vascular lesions according to the results. A smart bracelet was used to obtain the patient sleep data. The correlation between sleep patterns and diabetic lower-extremity atherosclerosis, diabetic foot, and various metabolic indices was verified.ResultsBetween August 2021 and April 2022, we screened 100 patients with type 2 diabetes, with 80 completing sleep monitoring. Univariate ordered logistic regression analysis indicated that patients with a sleep score below 76 (OR = 2.707, 95%CI: 1.127-6.488), shallow sleep duration of 5.3 h or more (OR=3.040, 95 CI: 1.005-9.202), wakefulness at night of 2.6 times or more (OR = 4.112, 95%CI: 1.513-11.174), and a deep sleep continuity score below 70 (OR = 4.141, 95%CI: 2.460-615.674) had greater risk of high-grade lower limb atherosclerosis. Multivariate ordinal logistic regression analysis revealed that the risk of high-grade lower limb atherosclerosis was higher in patients with 2.6 or more instances of nighttime wakefulness (OR = 3.975, 95%CI: 1.297-12.182) compared with those with fewer occurrences. The sleep duration curve of patients with different grades of diabetic lower-extremity atherosclerosis was U-shaped. According to the results of the one-way analysis of variance, the higher the deep sleep continuity score, the lower the Wagner scale score for diabetic foot (P < 0.05).ConclusionsSleep disorders (long, shallow sleep duration, frequent wakefulness at night, and poor continuity of deep sleep) can worsen lower limb atherosclerosis in patients with type 2 diabetes. This finding can provide a new method for medical professionals to prevent and treat diabetic lower-extremity vascular lesions.

Project description:BackgroundHeart failure and arrhythmias occur more frequently in patients with type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a prediabetic condition marked by elevated reactive oxygen species (ROS) and subclinical cardiovascular defects. Although multifunctional Ca2+ calmodulin-dependent protein kinase II (CaMKII) is ROS-activated and CaMKII hyperactivity promotes cardiac diseases, a link between prediabetes and CaMKII in the heart is unprecedented.ObjectivesTo prove the hypothesis that increased ROS and CaMKII activity contribute to heart failure and arrhythmogenic mechanisms in early stage diabetes.Methods-resultsEchocardiography, electrocardiography, biochemical and intracellular Ca2+ (Ca2+i) determinations were performed in fructose-rich diet-induced impaired glucose tolerance, a prediabetes model, in rodents. Fructose-rich diet rats showed decreased contractility and hypertrophy associated with increased CaMKII activity, ROS production, oxidized CaMKII and enhanced CaMKII-dependent ryanodine receptor (RyR2) phosphorylation compared to rats fed with control diet. Isolated cardiomyocytes from fructose-rich diet showed increased spontaneous Ca2+i release events associated with spontaneous contractions, which were prevented by KN-93, a CaMKII inhibitor, or addition of Tempol, a ROS scavenger, to the diet. Moreover, fructose-rich diet myocytes showed increased diastolic Ca2+ during the burst of spontaneous Ca2+i release events. Mice treated with Tempol or with sarcoplasmic reticulum-targeted CaMKII-inhibition by transgenic expression of the CaMKII inhibitory peptide AIP, were protected from fructose-rich diet-induced spontaneous Ca2+i release events, spontaneous contractions and arrhythmogenesis in vivo, despite ROS increases.ConclusionsRyR2 phosphorylation by ROS-activated CaMKII, contributes to impaired glucose tolerance-induced arrhythmogenic mechanisms, suggesting that CaMKII inhibition could prevent prediabetic cardiovascular complications and/or evolution.

Dataset Information

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

Background

Aims

Methods

Results

Conclusions

Publications

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

Similar Datasets

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