Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of Perilipin 5?

Abstract

Intramyocellular lipids (IMCL) hamper insulin sensitivity albeit not in endurance-trained athletes (Trained). Compared to type 2 diabetes patients (T2DM), Trained subjects have high levels of Perilipin 5 (PLIN5). Here, we tested if the fraction of PLIN5 coated LDs is a determinant of skeletal muscle insulin sensitivity and contributes to the athlete's paradox. Muscle biopsies were taken from 8 Trained, Lean sedentary, Obese and T2DM subjects. Trained, Obese and T2DM subjects were matched for total IMCL content. Confocal images were analysed for lipid area fraction, LD size and number and PLIN5+ and PLIN5- LDs were measured. A stepwise linear regression was performed to identify factors explaining observed variance in GIR. Trained and T2DM subjects stored IMCL differently; Trained had a higher number of LDs compared to T2DM (0.037 ± 0.004 μm⁻²vs. 0.023 ± 0.003 μm⁻², P = 0.024), that were non-significantly smaller (0.27 ± 0.01 μm²vs. 0.32 ± 0.02 μm², P = 0.197, Trained vs. T2DM). Even though total PLIN5 protein content was almost double in Trained vs. T2DM (1.65 ± 0.21 AU vs. 0.89 ± 0.09 AU, P = 0.004), PLIN5 coating did not affect LD number or size significantly. Of the observed variance in GIR, the largest fraction by far (70.2%) was explained by maximal oxygen uptake, adding PLIN5 protein content or PLIN5+ LDs increased the explained variance in GIR (74.7% and 80.7% for PLIN5 protein content and PLIN5+ LDs, respectively). Thus, the putative relation between PLIN5 and insulin sensitivity is at best indirect and is apparent only in conjunction with maximal oxygen uptake. Hence, PLIN5 abundance cannot be causally linked to the athlete's paradox.

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Local Oscillatory Properties of the Dendritic Membrane of Hippocampal Pyramidal Neurons: a Simulation Study

Foci of epileptic activity, generated as a result of synchronization of periodic burst discharges in neuronal networks, are often localized in the hippocampus. Using a model approach, we investigated the possibility of and biophysical conditions for the appearance of local oscillatory processes in dendrites possessing voltage-dependent channels (which is typical of pyramidal neurons of the hippocampus). The study was performed on a computer model of the membrane with active conductivities inherent in dendrites of pyramidal neurons of the CA3 area. It was found that such a membrane compartment subjected to tonic synaptic excitatory influences can function as a local generator of stable depolarization of a low or a high level or as a generator producing membrane potential oscillations (local oscillator). Each of these modes corresponds to a certain range of the synaptic excitation intensity; with increasing temperature, the range within which the oscillator properties are manifested is narrowed, while the range within which high-level stable depolarization is generated is expanded.

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EEG Activities and the Sustained Attention Performance

We investigated the relations between EEG activity and sustained attention in humans. A visual version of the conjunctive continuous performance task (CCPT-V) was used as a measure of sustained attention. Twenty university students voluntarily participated in the study; they were divided into two groups, good and weak, according to their results in the CCPT-V. The spectral power of EEG recorded from Fz, Cz, and Pz was analyzed under three conditions (eyes open, eyes closed, and CCPT-V) in four frequency ranges, theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–60 Hz) in three channels. Results of repeatedmeasures MANOVA showed the significance of the effects of conditions and channels with respect to the alpha and theta but not to the beta and gamma powers. There was no significant effect of the group, but, when comparing the alpha power under three conditions, the good group showed lower spectral powers. It has been concluded that cerebral neuronal systems producing alpha and theta oscillations play a role in sustained attention, and this can be shown by EEG recording and in the respective test.

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Cortical Visual Evoked Potentials in Subjects with Auditory Deprivation (Congenital Deafness)

In 30 healthy men (age 19–25 years) with normal hearing and 30 men of the same age suffering from complete congenital deafness, we examined peculiarities of the cortical visual evoked potentials, VEPs (photostimulation of the right and left eye by LED flashes, recording from loci O1 and O2). It was found that subjects with auditory deprivation demonstrated significantly shorter (P < 0.05–0.001) peak latencies of the early VEP components (P1, N2, and P2), while peak latencies of the late waves (N2 and P3) were greater (P < 0.05) than the corresponding indices in the control group. Peak-to-peak amplitudes of all VEP components in deaf subjects were about two to three times lower than those in subjects with normal hearing (P < 0.05–0.001). The mean total duration of the VEPs in deaf persons was significantly greater than in the control group (P < 0.05). Therefore, loss of the auditory function in deaf subjects results, due to cross-modal transformations, in substantial modifications of the potentials reflecting perception of the visual signals.

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Inhibitors of Poly(ADP-Ribose)Polymerase-1 as Agents Providing Correction of Brain Dysfunctions Induced by Experimental Diabetes

The effects of 1,5-isoquinolinediol (IQD) and nicotinamide (NAm), inhibitors of poly-(ADP-ribose) polymerase-1 (PARP-1), on inflammatory processes and activation of PARP-1 under conditions of the development of experimental diabetic neuropathy, DN (a complication of streptozotocin-induced type-1 diabetes) in rats were studied. The content of IL-4 in blood serum in the case of DN was 50% higher, while that of monocyte-chemotactic protein-1 was 90% higher than those in the control. The content of gamma-interferon also increased, while the content of the granulocyte-macrophage colony-stimulating factor did not change. Against the background of activation of PARP-1 and a decrease in the content of the substrate of this enzyme nicotinamide adenine dinucleotide (NAD) in the brain, fragmentation of PARP-1 was intensified; an increase in the ratio of the contents of a 89 kDa fragment/intact enzyme molecules proved this fact. The mentioned two structurally dissimilar PARP-1 inhibitors partly or entirely normalized the above parameters under DN conditions. These results demonstrate that PARP-1 is one of the main functional targets in realization of the effects of IQD and NAm. At the same time, the spectrum of action of these inhibitors is wider. In particular, they affect the level of proinflammatory cytokines. The ability of the investigated PARP-1 inhibitors to prevent cell death in the brain by suppressing activation and fragmentation of the above-mentioned enzyme shows that other types of action of these agents at the molecular level are possible; these may be the maintenance of the genome integrity in the brain structures under DN conditions and preventing the development of inflammatory processes. Thus, the examined inhibitors can be used in the future in the treatment of brain dysfunctions that are complications of type-1 diabetes mellitus.

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Cerebral Activities in Rats within Different Periods after Experimental Unilateral Cerebral Ischemia

A model of cerebral ischemia in the left hemisphere was established in rats by occlusion of the left middle cerebral artery (MCAO). Twenty-five Sprague-Dawley rats were divided into five groups, the control (C) group and animals 4, 24, 48h, and one week (4h, 24h, 48h, and 1w, respectively) after MCAO. The footprint pattern test (FPT) was used to compare the gait in the MCAO groups with that in the C group. Ongoing EEGs were recorded and analyzed (spectral power densities of different rhythms were calculated). Somatosensory evoked potentials (SSEPs) were induced by stimulation of the right median nerve and averaged. Rats of group 4h displayed significantly worse gait parameters compared to those in the C group (P < 0.01). The 24h, 48h, and 1w groups demonstrated no significant differences from this aspect, as compared with the C group (P > 0.05). Compared with the latter group, mean EEG mean powers of the EEG rhythms in the MCAO groups were significantly lower (P < 0.01), latencies of the SSEP components were longer, and peak amplitudes were reduced significantly (P < 0.01). All EEG and SSEP parameters demonstrated trends toward normal values with increase in the time interval after MCAO but were not restored completely. Therefore, functional behavioral tests, EEG, and SSEP monitoring at different phases after experimental cerebral ischemia can provide detailed valuable information on the states of neural activities, which are well correlated with the motor function recovery.

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Ethical Responsibilities of The Authors

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