Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome.

Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.

Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19.

We evaluated associations between serum 25-hydroxyvitamin D [25(OH)D] level and severity of new coronavirus infection (COVID-19) in hospitalized patients. We assessed serum 25(OH)D level in 133 patients aged 21-93 years. Twenty-five (19%) patients had severe disease, 108 patients (81%) had moderate disease, and 18 (14%) patients died. 25(OH)D level ranged from 3.0 to 97.0 ng/mL (median, 13.5 [25%; 75%, 9.6; 23.3] ng/mL). Vitamin D deficiency was diagnosed in 90 patients, including 37 with severe deficiency. In patients with severe course of disease, 25(OH)D level was lower (median, 9.7 [25%; 75%, 6.0; 14.9] ng/mL), and vitamin D deficiency was more common than in patients with moderate course (median, 14.6 [25%; 75%, 10.6; 24.4] ng/mL, p = 0.003). In patients who died, 25(OH)D was 9.6 [25%; 75%, 6.0; 11.5] ng/mL, compared with 14.8 [25%; 75%, 10.1; 24.3] ng/mL in discharged patients (p = 0.001). Severe vitamin D deficiency was associated with increased risk of COVID-19 severity and fatal outcome. The threshold for 25(OH)D level associated with increased risk of severe course was 11.7 ng/mL. Approximately the same 25(OH)D level, 10.9 ng/mL, was associated with increased risk of mortality. Thus, most COVID-19 patients have vitamin D deficiency; severe vitamin D deficiency is associated with increased risk of COVID-19 severity and fatal outcome.

Comparative evaluation of metformin and liraglutide cardioprotective effect in rats with impaired glucose tolerance.

Impaired glucose tolerance (IGT) increases cardiovascular risk and can enlarge myocardial infarction (MI) incidence and severity. There is lack of information about cardioprotective potential of glucose-lowering drugs in IGT. We aimed to evaluate the sustainability of myocardium to ischemia-reperfusion injury in diabetic and IGT rats and to study cardioprotective action of metformin and liraglutide. Type 2 diabetes mellitus (DM) and IGT were modelled in Wistar rats by high-fat diet and streptozotocin + nicotinamide. 4 weeks after rats were divided into 4 groups: DM (without treatment) (n = 4), IGT (without treatment) (n = 4), IGT + MET (metformin 200 mg/kg per os once daily 8 weeks) (n = 4), IGT + LIRA (liraglutide 0.06 mg/kg s.c. once daily for 8 weeks) (n = 4). Control (n = 6) and high-fat diet (n = 8) groups were made for comparison. After 8 weeks ischemia-reperfusion injury in isolated hearts was performed. Hemodynamic parameters were evaluated and MI size was measured by staining of myocardium slices in triphenyltetrazolium chloride solution. Blood glucose level was measured during the study. Both IGT and DM led to similar worsening of hemodynamic parameters during ischemia-reperfusion period, in comparison with control group. MI size in IGT (56.76 (51.58; 69.07) %) and DM (57.26 (45.51; 70.08) %) groups was significantly larger than that in control group (42.98 (33.26; 61.84) %) and did not differ between each other. MI size in high-fat diet group (56.98 (47.11; 62.83) %) was as large as in IGT and DM groups (p > 0.05). MI size in IGT + MET (42.11 (38.08; 71.96) %) and IGT + LIRA (42.50 (31.37; 60.40) %) was smaller than in both DM and IGT groups (p < 0.05 for multiple comparison). Myocardium damage size did not differ in IGT + MET and IGT + LIRA groups (p >  0.05). Only LIRA, but not MET administration to IGT rats led to ischemic contracture reduction. Glycemic control was similarly satisfactory in IGT, IGT + MET, IGT + LIRA groups. Thus, IGT and DM have similarly pronounced negative influence on hemodynamics and MI size in rat transient global ischemia ex vivo. Obesity development also has negative impact on the MI size. Both MET and LIRA have infarct-limiting effect independent on their influence on glucose level. LIRA, but not MET, diminishes ischemic contracture in IGT rats.

Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity.

RATIONALE: It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. PURPOSE: To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. METHODS: The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients' evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. RESULTS: Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss ≥ 5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. CONCLUSION: The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.

Neuroprotective effect of glucagon-like peptide-1 receptor agonist is independent of glycaemia normalization in type two diabetic rats.

OBJECTIVE: Stroke is a severe complication of type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists have been shown to have a neuroprotective effect in experimental diabetes. The aim of this study was to determine if their neuroprotective effect is an independent property of the drug independent of glycaemic control. METHODS: This two-phase study used male Wistar rats. In the first phase, experimental animals were pretreated with liraglutide, while controls received only vehicle. After transient focal brain ischaemia modelling, neurological deficit and brain infarct volume were measured. In the second phase, the first and the second groups of experimental animals with type 2 diabetes mellitus received liraglutide and metformin, respectively, while control animals with diabetes received only vehicle. After transient focal brain ischaemia modelling, neurological deficit and brain infarct volume were evaluated. RESULTS: Pretreatment with liraglutide in diabetic and non-diabetic animals reduced infarct size as compared to controls, while only non-diabetic liraglutide-treated rats presented neurologic deficit decreases. Despite glycaemia normalization, metformin-treated diabetic rats had no differences in stroke outcome when compared to the control group. CONCLUSION: The neuroprotective effect of liraglutide is not associated with glycaemic control amelioration in experimental type 2 diabetes mellitus.

L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion.

While the neuroprotective effect of green tea (Camellia sinensis) might be explained by the presence of amino acid L-theanine in the tea leaves, it is not known whether postischemic administration of L-theanine could also provide neuroprotection. In the present study, we investigated the neuroprotective effect of L-theanine (1 and 4 mg/kg) administered at 3, 12, and 24 h after reperfusion in the rat model of stroke. We also studied the effect of L-theanine on brain injury caused by exogenous administration of N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate receptor agonists during reperfusion. Rats were subjected to 30-min middle cerebral artery occlusion followed by 48-h reperfusion. Neurological deficit and infarct size were determined at the end of reperfusion. At 3 and 12 h, but not at 24 h of reperfusion, L-theanine substantially reduced the size of brain infarct. Neurological status was improved when L-theanine was administered 3, 12, and 24 h after reperfusion. Repeated intrastriatal injections of L-theanine at a total dose of 800 µg/kg during reperfusion prevented brain injury caused by glutamate receptor agonists. In conclusion, L-theanine at reperfusion exerts neuroprotective effect in the in vivo rat model of stroke. Local treatment with L-theanine at reperfusion prevents glutamate receptor agonist-mediated brain injury.