Original Data
| Rev Diabet Stud,
2012,
9(2-3):94-103 |
DOI 10.1900/RDS.2012.9.94 |
Effect of Short-Term Hyperglycemia on Protein Kinase C Alpha Activation in Human Erythrocytes
Leonid Livshits1, Ariel Srulevich1, Itamar Raz1, Avivit Cahn2, Gregory Barshtein3, Shaul Yedgar3, Roy Eldor1
1The Diabetes Research Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel
2Endocrinology and Metabolism Service, Hadassah Hebrew University Medical Center, Jerusalem, Israel
3Department of Biochemistry, Hadassah Hebrew University Medical Center, Jerusalem, Israel
Address correspondence to: Leonid Livshits, The Diabetes Research Center, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel, e-mail: leonidlivshts@gmail.com
Abstract
BACKGROUND: Diabetes mellitus, characterized by chronic hyperglycemia, is known to have a deleterious effect on erythrocyte structure and hemodynamic characteristics, which eventually contribute to diabetes-associated vascular complications. Protein kinase C alpha (PKCα) is a major regulator of many metabolic processes and structural changes in erythrocytes, and may play a significant role in the development of hyperglycemia-mediated cellular abnormalities. AIM: We hypothesized that acute hyperglycemic stress may affect erythrocyte structure and metabolic properties through its effect on PKCα membrane content and activity. RESULTS: Erythrocytes, from healthy individuals acutely exposed to a glucose enriched media, showed a significant decrease in the membranous fraction of PKCα and its phosphorylation (p = 0.005 and p = 0.0004, respectively). These alterations correlated with decreased affinity of PKCα to its membrane substrates (4.1R and GLUT1) and reduced RBC deformability (p = 0.017). Pre-activation of erythrocytes with PKC activator, PMA, minimized the effect of glucose on the membrane PKCα fraction and RBC deformability (p > 0.05). CONCLUSIONS: Acute glycemia-induced inhibition of PKCα membranous translocation and activation is associated with reduced erythrocyte membrane deformability.
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| Rev Diabet Stud,
2012,
9(2-3):104-111 |
DOI 10.1900/RDS.2012.9.104 |
Orbital Doppler Evaluation of Blood Flow Velocities in Patients with Diabetic Retinopathy
Mehdi Karami1, Mohsen Janghorbani2, Alireza Dehghani3, Karim Khaksar1, Ahmad Kaviani1
1Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
3Department of Ophthalmology, Feiz Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
Address correspondence to: Mohsen Janghorbani, e-mail: janghorbani@hlth.mui.ir
Abstract
BACKGROUND: There have been conflicting results in relation to impaired ocular hemodynamics in the orbital vessels of patients with diabetic retinopathy (DR). Clarification of the early signs of retinopathy in diabetic patients is urgently needed. AIMS: We aimed to evaluate orbital blood flow velocities using Doppler and gray-scale sonography in patients with DR, and to compare the results with those of their non-diabetic and diabetic peers without retinopathy. METHODS: Orbital Doppler and gray-scale sonography were performed in 123 patients aged 29-77 who had been divided into 3 groups: non-diabetic controls (n = 25), diabetes and impaired glucose tolerance with minimal clinical retinopathy (n = 74), and diabetes with untreated non-proliferative retinopathy (n = 24). Retinopathy was diagnosed by an ophthalmologist on the basis of fundoscopic examination. The peak systolic (PSV) and end-diastolic (EDV) blood flow velocities, and the resistivity and pulsatile indices, of the ophthalmic artery, central retinal artery, posterior ciliary artery, and central retinal vein were measured. RESULTS: Compared with healthy controls, the age-adjusted resistivity and pulsatile indices of the ophthalmic artery were significantly higher in patients with DR (p < 0.05). PSV and EDV of the posterior ciliary arteries were significantly lower in diabetic patients with DR. After further adjustment for age, gender, HbA1c, fasting plasma glucose, blood pressure, BMI, cholesterol, HDL, LDL, and triglycerides, only the resistivity index of the ophthalmic artery and the central retinal vein remained significantly higher in patients with DR compared with healthy controls (p < 0.005 after Bonferroni adjustment). CONCLUSIONS: Resistivity index alteration of the ophthalmic artery and central retinal vein may be prevalent among patients with early changes in DR.
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| Rev Diabet Stud,
2012,
9(2-3):112-122 |
DOI 10.1900/RDS.2012.9.112 |
The rs11705701 G>A Polymorphism of IGF2BP2 is Associated With IGF2BP2 mRNA and Protein Levels in the Visceral Adipose Tissue - A Link to Type 2 Diabetes Susceptibility
Dimitry A. Chistiakov1, Alexey G. Nikitin2, Svetlana A. Smetanina3, Larisa N. Bel'chikova3, Lyudmila A. Suplotova3, Marina V. Shestakova4, Valery V. Nosikov2
1Pirogov Russian State Medical University, 117997 Moscow, Russia
2National Research Center GosNIIgenetika, 117545 Moscow, Russia
3Tyumen State Medical Academy, 625023 Tyumen, Russia
4Endocrinology Research Center, 117036 Moscow, Russia
Address correspondence to: Dimitry A. Chistiakov, Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Ulitsa Ostrovityanova 1, 117997 Moscow, Russia, e-mail: dimitry.chistiakov@lycos.com
Abstract
BACKGROUND: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) regulates translation of IGF2, a growth factor that plays a key role in controlling fetal growth and organogenesis including adipogenesis and pancreatic development. In Caucasians, the rs4402960 G>T polymorphism of IGF2BP2 has been shown to predispose to type 2 diabetes (T2D) in multiple populations. In this study, we tested whether rs4402960 G>T and rs11705701 G>A contribute to the development of T2D in a Russian population. METHODS: Both markers were genotyped in Russian diabetic (n = 1,470) and non-diabetic patients (n = 1,447) using a Taqman allele discrimination assay. The odds ratio (OR) for the risk of developing T2D was calculated using logistic regression assuming an additive genetic model adjusted for age, sex, HbA1c, hypertension, obesity, and body mass index (BMI). Multivariate linear regression analyses were used to test genotype-phenotype correlations, and adjusted for age, sex, hypertension, obesity, and BMI. Expression of IGF2BP2 in the visceral adipose tissue was quantified using real-time PCR. The content of IGF2BP2 protein and both its isoforms (p58 and p66) in the adipose tissue was measured using Western blot analysis. RESULTS: There was no significant association between rs4402960 and T2D. Whereas, allele A of rs11705701 was associated with higher T2D risk (OR = 1.19, p < 0.001). Diabetic and non-diabetic carriers of genotype TT (rs4402960) had significantly increased HOMA-IR (p = 0.033 and p = 0.031, respectively). Non-diabetic patients homozygous for AA (rs11705701) had higher HOMA-IR (p = 0.04), lower HOMA-β (p = 0.012), and reduced 2-h insulin levels (p = 0.016). Non-obese individuals (diabetic and non-diabetic) homozygous for either AA (rs11705701) or TT (rs4402960) had higher levels of IGF2BP2 mRNA in the adipose tissue than other IGF2BP2 variants. Also, allele A of rs11705701 was associated with reduced amounts of the short isoform (p58) and increased levels of the long isoform (p66) of the IGF2BP2 protein in adipose tissue of non-obese diabetic and non-diabetic subjects. CONCLUSIONS: IGF2BP2 genetic variants contribute to insulin resistance in Russian T2D patients. The short protein isoform p58 of IGF2BP2 is likely to play an anti-diabetogenic role in non-obese individuals.
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