Tag Archives: type 2 diabetes
Vitamin D(3) auto-/paracrine system in rat brain relating to vitamin D(3) status in experimental type 2 diabetes mellitus
I. Shymanskyi1*, O. Lisakovska1, A. Khomenko1,
L. Yanitska2, M. Veliky1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine;
2Bogomolets National Medical University, Kyiv, Ukraine;
*e-mail: ihorshym@gmail.com
Received: 29 January 2024; Revised: 08 March 2024;
Accepted: 11 March 2024; Available on-line: 30 April 2024
Growing evidence suggests that vitamin D3 (D3, cholecalciferol) deficiency and impaired signaling of the hormonally active form of D3, 1α,25(OH)2D3 (1,25D3), through its cellular receptor (VDR) can be significant risk factors for the development of numerous multifactorial diseases, including diabetes. Our investigation was aimed at researching the D3 status in relation to the state of the D3 auto-/paracrine system in the brain and clarifying the effectiveness of the therapeutic use of D3 as a neuroprotective agent in experimental type 2 diabetes mellitus (T2DM). T2DM was induced in male Wistar rats by a combination of a high fat diet and a low dose of streptozotocin (25 mg/kg BW). Diabetic animals were treated with or without cholecalciferol (1,000 IU/kg BW, 30 days). The content of 25-hydroxyvitamin D3 (25D3) in blood serum and brain tissue was determined by ELISA. Analysis of mRNA expression of CYP24A1 and CYP27B1 genes was performed by RT-PCR. Protein levels of VDR, vitamin D3 binding protein (VDBP), CYP27B1 and CYP24A1 were investigated by Western blotting. A significant T2DM-associated decrease in the content of 25D3 in the blood serum was revealed, which correlated with a reduced content of this metabolite in the brain tissue. Impaired D3 status in animals with T2DM was accompanied by an increase in the levels of mRNA and protein of both 25D3 lα-hydroxylase (CYP27B1) and 1,25-hydroxyvitamin D3-24-hydroxylase (CYP24A1), which, respectively, provide local formation and degradation in the nervous tissue of the hormonally active form of D3 – 1,25D3. At the same time, a significant T2DM-induced down-regulation of the brain content of VDBP was shown. In addition, diabetes caused a slight increase in the protein expression of the VDR, through which the auto-/paracrine effects of 1,25D3 are realized in the brain. We have established a complete or partial corrective effect of cholecalciferol on D3 status, its bioavailability in the CNS and the level of protein expression of CYP27B1 and CYP24A1 in the brain of rats with T2DM. Abnormal D3 status in animals with T2DM was accompanied by compensatory changes in the expression of key components of the auto-/paracrine vitamin D3 system. Cholecalciferol was demonstrated to be partially effective in counteracting the impairments caused by T2DM.
Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes
T. S. Vatseba1*, L. K. Sokolova2, V. M. Pushkarev2,
O. I. Kovzun2, B. B. Guda2, V. V. Pushkarev2,
M. D. Tronko2, N. V. Skrypnyk1, L. M. Zaiats1
1Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine;
2SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv;
*e-mail: tamara.vatseba@gmail.com
Received: 17 April 2020; Accepted: 13 November 2020
Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes.
Hypertriglyceridemia is associated with long-term risk of cardiovascular events and specific comorbidity in very high-risk hypertensive patients
O. Ya. Korolyuk, O. M. Radchenko
Danylo Halytskyi Lviv National Medical University, Department of Internal Medicine No 2, Lviv, Ukraine;
e-mail: korolyukolga7619@gmail.com
Received: 19 December 2019; Accepted: 27 March 2020
Although hypertriglyceridemia (HTG) frequently occurs in hypertensive patients and may increase cardiovascular risk, the need for and manner of its reduction remain controversial. The objectives of this study were to compare lipid profiles, parameters of glucose homeostasis, comorbidity, and 5-year survival without cardiovascular events in very high-risk hypertensive (VHRH) patients with and without HTG, who received moderate intensity atorvastatin therapy. After initial assessment, 107 VHRH subjects were divided into two groups, i.e., without (n = 49) and with HTG (n = 58). During observation once annually patients were interviewed about prior hospitalizations with further screening for diabetes. Combined endpoint included hospitalization due acute myocardial infarction, decompensated heart failure, stroke or death. Survival was analyzed by Kaplan-Meier’s method. Nonparametric methods were used for statistical analysis. Higher median values of logarithmic value of triglycerides-to-HDL-cholesterol ratio, lipid accumulation product, fasting insulin, and HOMA index were observed in group 2 (P < 0.002) that reflect predominance of small dense LDL particles, ectopic lipid deposition and insulin resistance. Patients with HTG more commonly had type 2 diabetes (58.6% vs 34.5%, including first-detected cases during initial assessments and observation, P = 0.02), liver steatosis (81.0% vs 55.1%, P = 0.006), and lithogenic gallbladder disorders (55.2% vs 34.7%, P=0.05). Women with HTG frequently had a history of hysterovariectomy (55.2% vs 19.0%, Р = 0.018). Despite long-term statin therapy, they often failed to reach recommended LDL-C targets and had worse survival due to significantly higher incidence of combined endpoint (39.6% vs 22.4%, P = 0.027). Further studies are necessary to find safe and effective strategy for secondary prevention in this population.
Cardiovascular disease among patients with type 2 diabetes: role of homocysteine as an inflammatory marker
Ashok Sahu1,2, Trapti Gupta2, Arvind Kavishwar3, R. K. Singh4
1MGM Medical College Indore, Jabalpur, India;
e-mail: asahu888@gmail.com; asahu888@yahoo.co.in;
2NSCB Medical College, Jabalpur, India;
3Regional Malaria Research Centre of Tribal (ICMR), Jabalpur, India;
4Chirayu Hospital, Bhopal, India
It is known that inflammation has a role in the pathogenesis of cardiovascular diseases; measurement of inflammatory markers improves the risk prediction of cardiovascular diseases. Hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks and strokes; though it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions. In the present study, we aimed to evaluate the role of homocysteine in type 2 diabetes patients with cardiovascular disease in a population of Madhya Pradesh India. Total 100 type 2 diabetes patients were included in the study, of these 50 had angiographically proven cardiovascular disease and 50 had no evidence of it. High sensitivity C-reactive protein, fibrinogen, and lipoprotein (a) were measured in serum. Homocysteine, blood glucose in plasma, erythrocyte sedimentation rate, glycated haemoglobin were measured in whole blood. A albumin excretion rate, creatinine clearance rate were measured in the urine sample for renal function. It was shown that, levels of homocysteine and other inflammatory markers were elevated significantly in the group II (n = 50). A correlation between hyperhomocysteinemia and inflammatory markers in patients with impaired renal function was observed. It was concluded that impairment of renal function is a key factor that affects homocysteine level.