Iranian Journal of Diabetes and Lipid Disorders

ASSOCIATION OF KILLER IMMUNOGLOBULIN IIKE RECEPTOR (KIR) GENE POLYMORPHISMS WITH TYPE 1 DIABETES: A META-ANALYSIS

English version of this article has been published in “ journal of diabetes & metabolic disorders “ with both editor-in-chiefs agreement; aims to be available for Persian language readers; http://doi.org/10.1111/j.1399-039.2007.00956.x.

THE EFFECT OF HIGH-INTENSITY INTERVAL TRAINING (HIIT) WITH AND WITHOUT CAFFEINE INJECTION ON EXPRESSION OF MYOCARDIAL AUTOPHAGY-RELATED PROTEINS IN DIABETIC RATS

Afshar Jafari

Background: Autophagy is a new therapeutic strategy aimed at reducing the diabetic abnormalities. While excessive or insufficient autophagic activity during diabetes leads to altered cellular homeostasis. So, aim of the present study was conducted to determine the effect of eight-week high-intensity interval training (HIIT) along with caffeine injection on the levels of some myocardial autophagy-related proteins in diabetic rats.
Methods: In experimental design, fifty male white wistar rats with an age range of 3-2 months (average weight 250±25 g) were randomly divided into 5 groups of homogeneous 10 rats in each group: Healthy control (C: intraperitoneal injection of saline), Diabetic control (D: high-fat diet combined with a single intraperitoneal injection of streptozotocin, Diabetic with training (D+T: running with intensity at the 85-90% of maximum speed in 5 to 12 bout of 2 min^-1; 5 days/week for 8 weeks), Diabetic with caffeine supplementation(D+CA: intraperitoneal injection of pure caffeine at 70 mg.kg^-1 5 days/week for 8 weeks), Diabetic with training and with caffeine supplementation (D+T+CA). For evaluate changes in the expression profile of some of the genes associated with autophagy signaling pathway (LC3-II, ULK-1, Beclin1) in the myocardium (left ventricular), based on Western blot analysis will be used. Also, the one-way analysis of variance (ANOVA) and Tukey post hoc test were be used to analyze the data.
Results: The expression of all autophagic proteins in diabetic with trained and non-trained groups was higher than in healthy
group (P≤0.05). On the one hand, the expression of autophagy-related proteins in the trained group with caffeine supplementation was significantly higher than that of the training group without caffeine intake (P=0.001).
Conclusion: The findings of this study suggest that caffeine injection exacerbated the expression of autophagic proteins induced by diabetes; On the other hand, high-intensity interval training can as a preventive strategy, modulate diabetes-induced myocardial autophagy.

CHANGES OF PERK AND CHOP PROTEINS IN ENDOPLASMIC RETICULUM OF CARDIAC MYOCYTES AND TNF IN DIABETIC WISTAR RATS FOLLOWING CONTINUOUS AND INTERVAL EXERCISE

Hasan Matinhomaie

Background: Physical activity plays a major role in the prevention of cardiovascular disease and diabetes, but the effect of intense activity on endoplasmic reticulum proteins and apoptosis and necroptosis in diabetic conditions is unclear. The aim of the present study was to investigate the changes of PERK and CHOP proteins in endoplasmic reticulum of cardiac myocytes of diabetic Wistar rats following continuous and interval exercise.
Methods: For this purpose, 32 male white wistar were purchased and were randomly divided into 4 groups of hemogenus 8 rats in each group: Healthy control (C), Diabetic control (D), Diabetic with moderate-intensity continuous training intensity at the 55min on 26 m/min speed (D+MICT) and Diabetic with high-intensity interval training intensity at the 85-90% of maximum speed (D+HIIT); 5 days/week for 8 weeks. For evaluate changes in the expression of the proteins associated with apoptosis and necroptotic death in the diabetic heart muscle myocardium, based on Western blot analysis will be used. Also, the one-way analysis of variance (ANOVA) is used to determine differences between the study groups.
Results: The results showed that induction of type 2 diabetes increased apoptotic and necroptosis cell death (P≥0.05). Therefore, both continuous and intermittent aerobic exercise modulate apoptotic cell death. And both intermittent and continuous exercise had a significant effect on cell necroptosis death.
Conclusion: It seems that different levels of aerobic exercise have different effects on cardiac myocytes cell death in diabetic rats. But more research is needed to confirm the death of diabetic necroptics.

EVALUATION OF METABOLIC PROFILE OF PLASMA AMINO ACIDS IN DIABETIC PATIENTS WITH CARDIOVASCULAR DISEASES

Esmail Shekari

Background: Diabetes mellitus is one of the most common endocrine diseases. Cardiovascular disease (CVD) is one of the leading causes of death in patients with type 2 diabetes. The aim of this study was to investigate the metabolic profile of plasma amino acids in diabetic patients with cardiovascular disease.
Methods: The present study is a descriptive-analytical cross-sectional study on 140 patients including 35 patients with type 2 diabetes and cardiovascular disease (CVD.DM), 35 patients with type 2 diabetes and non-cardiovascular disease (DM). 35 non-diabetic patients with cardiovascular disease (CVD.nDM) and 35 non-diabetic patients with non-cardiovascular disease (HS) were referred to Diabetes Clinic No. 1 of Tehran University of Medical Sciences.
Results: 76 (54.3%) were male and 64 (45.7%) were female. The highest concentrations of glutamine and isoleucine were observed in DM.CVD, asparagine, serine, arginine, threonine, alanine, tyrosine, valine in DM.nCVD and methionine in CVD.nDM. The lowest concentrations of tyrosine and tryptophan in DM.CVD has been detected , and methionine has been detected in DM.nCVD. The amino acids alanine, glutamine, tyrosine, valine, methionine, leucine, lysine and arginine significantly increased the chances of developing DM.nCVD. For each increase in Z-score per plasma concentration of isoleucine, the chances of developing cardiovascular disease without diabetes were significantly increased.
Conclusion: The amino acids alanine, glutamine, tyrosine, valine, methionine, leucine, lysine and arginine are involved in predicting the risk of DM.nCVD and isoleucine and methionine are involved in predicting the risk of CVD.nDM.

INVESTIGATING THE ROLE OF MTNR1B RS4753426 GENETIC VARIANT IN THE TYPE 2 DIABETES MELLITUS RISK

Mandana Hasanzad

Background: Type 2 diabetes Mellitus (T2DM) is a multifactorial, polygenic disease caused by impaired insulin secretion, insulin resistance and beta-cell dysfunction. Melatonin is a circadian rhythm regulator and any imbalance in its levels can be related to various metabolic disorders. Melatonin and the genetic variants of MTNR1B gene are reported to be associated with T2DM susceptibility. We investigated the association between rs4753426 variant in the MTNR1B gene and the risk of T2DM in group of Iranian patients.
Methods: In this case-control study108 T2DM and 100 normal individuals were recruited to genotyping by PCR- RFLP.
Results: It was observed a significant difference in CC, CT, and TT genotypes distribution between T2DM and control groups (P<0.001). Frequency of C allele among cases was significantly lower than controls (8.3% vs. 42.5% respectively, P<0.001) and C allele carriers had a 88% lower risk of developing T2DM than T carriers.
Conclusion: Our results showed that the rs4753426 variant of MTNR1B gene could reduce the risk of T2DM developing.

BIOINFORMATIC STUDY ON EFFECT OF XANTHOHUMOL AS BIOACTIVE COMPOUND OF HOP IN THE INHIBITION OF THE MAPK/ERK PATHWAY IN THYROID CANCER

Vahid Haghpanah

Background: Xanthohumol is one of the main bioactive compounds extracted from the female flowers of the hops plant (Humulus lupulus L), that has been shown in several studies to have anti-cancer effects.The MAPK/ERK pathway is one of the key pathways in the regulation of gene expression, cell growth and survival. The abnormal activation of this pathway leads to the uncontrolled cell proliferation in thyroid cancer. This study aims to perform a bioinformatic screening of the proteins in the MAPK/ERK pathway and introduce them as target protein to Xanthohumol. In addition, due to the significant role of EGFR, Grb2, SOS proteins in the MAPK/ERK pathway, they have also been studied.
Method: Using SwissADME software, first the physicochemical, pharmacokinetic and pharmacodynamic characteristics of Xanthohumol are predicted. Then three-dimensional structure of Xanthohumol and target proteins (EGFR, Grb2, SOS, RAS, BRAF, MEK1, MEK2, ERK1, ERK2) were collected from PubChem database and Protein Data Bank, finally, using Auto Dock 4.1.the molecular docking were studied.
Results: Our study shows lack of cytotoxicity in Xanthohumol. In addition, Xanthohumol with proper physicochemical properties does not induce drug resistance through pump P-glycoprotein mechanism. Analysis of molecular docking indicate that Xanthohumol has inhibitory potential to the all proteins studied. Note that its strongest interaction is with MEK2 protein with binding energy-7.04kcal.mol^-1.
Conclusion: According to our results, Xanthohumol has inhibitory potential to the all proteins present in the MAPK/ERK pathway. It lacks cytotoxicity. Thus, it can be considered as an alternative inhibitor for the MAPK/ERK pathway in thyroid cancer cells.