Long-term GABA administration improves FNDC5, TFAM, and UCP3 mRNA expressions in the skeletal muscle and serum irisin levels in chronic type 2 diabetic rats.

In this study, we aimed to investigate whether the anti-diabetic effects of γ-aminobutyric acid (GABA) and insulin can be mediated through the regulation of gene expression related to irisin production and mitochondrial biogenesis in type 2 diabetic mellitus (T2DM) rats. Four groups (n = 6) were used in this study: control, T2DM, T2DM + insulin, and T2DM + GABA groups. After T2DM induction for 3 months (high-fat diet + 35 mg/kg streptozotocin) and treatment with GABA or insulin for 3 months, circulating levels of FBG, triglyceride, LDL, Ox-LDL, and insulin as well as hepatic and serum irisin levels were measured. The mRNA expressions of fibronectin type III domain-containing protein 5 (FNDC5), mitochondrial transcription factor A (TFAM), and mitochondrial uncoupling protein 3 (UCP3) were also evaluated in the skeletal muscle of all groups. GABA therapy improved the FBG and insulin levels in diabetic rats. Insulin treatment significantly reduced FBG and failed to maintain glucose close to the control level. Insulin or GABA therapy significantly decreased the levels of LDL, Ox-LDL, and HOMA-IR index. Circulating irisin levels were markedly decreased in insulin-treated group, while irisin levels did not show significant changes in GABA-treated group compared with control group. GABA or insulin therapy increased mRNA expressions of TFAM and UCP3 in diabetic rats. GABA therapy also led to a significant increase in FNDC5 mRNA. Our findings suggest that the anti-diabetic effect of GABA may be mediated, in part, by a decrease in Ox-LDL levels and an increase in the levels of irisin as well as FNDC5, TFAM, and UCP3 gene expression in T2DM rats.

Beneficial effects of MgSO4 on TFAM, UPC3 and FNDC5 mRNA expressions in skeletal muscle of type 2 diabetic rats: a possible mechanism to improve insulin resistance.

BACKGROUND: Hypomagnesemia has been associated with development of type 2 diabetes mellitus (T2DM) and its complications. Irisin has beneficial effects on glucose uptake and improves hepatic glucose and lipid metabolism. In this study, we aimed to evaluate the effects of long-term treatment of MgSO4 and insulin on insulin resistance, dyslipidemia, serum and hepatic irisin levels, skeletal muscle gene expression of fibronectin type III domain-containing protein 5 (FNDC5), mitochondrial transcription factor A (TFAM) and mitochondrial uncoupling protein 3 (UCP3) in T2DM rats. METHODS AND RESULTS: Twenty-four rats were divided into four groups: Control group, diabetic control (DC) using a high-fat diet + streptozotocin, insulin-treated diabetic group (DC + Ins), MgSO4-treated diabetic group (DC + Mg). At the end of therapies, serum concentrations of FBG, TG, insulin, Ox-LDL, along with serum and hepatic irisin levels were measured. FNDC5, TFAM, and UCP3 mRNA expressions were measured in the skeletal muscle by Real-time PCR. In comparison with DC group, MgSO4 therapy resulted in decreased FBG, TG, Ox-LDL, improved serum insulin and irisin levels, and increased mRNA expressions of FNDC5, UCP3 and TFAM. Insulin therapy significantly decreased FBG, Ox-LDL, FNDC5 and serum irisin levels compared with the control group. While, insulin therapy markedly increased TFAM and UCP3 compared with the DC group. CONCLUSIONS: In conclusion, MgSO4 can improve insulin resistance and hyperlipidemia partly through decreasing Ox-LDL, increasing serum irisin levels as well as increasing FNDC5, TFAM, and UCP3 mRNA expressions in T2DM rats. These findings can be considered in the management of diabetes treatment.

Determination of plasma and erythrocyte levels of copper, magnesium and zinc by atomic absorption spectrometry in type-2 diabetes mellitus patients with metabolic syndrome.

BACKGROUND AND PURPOSE: Imbalance in blood levels of trace elements is independent risk factor for metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and its complications. This study investigated plasma and erythrocyte levels of copper, magnesium, zinc, and their correlations with biochemical components of the MetS in T2DM patients compared to the healthy controls. EXPERIMENTAL APPROACH: Forty men recently diagnosed T2DM with MetS without complications and thirty six age-matched healthy controls were enrolled in this cross-sectional study. Plasma and erythrocyte levels of selected elements were measured by graphite furnace atomic absorption spectroscopy. FINDINGS/RESULTS: The results of the present study showed significantly lower plasma levels of copper, magnesium, and zinc and lower erythrocytes copper in the patients' group compared to the controls; while erythrocyte levels of magnesium and zinc were not significantly different between the two groups. Significant negative correlations were observed between plasma levels of copper with waist and hip circumferences, waist to hip ratio, systolic and diastolic blood pressures, fasting blood glucose, and glycated hemoglobin levels in all subjects; while erythrocyte copper levels showed significant negative correlation with triglyceride, and erythrocyte zinc was positively correlated with diastolic blood pressure and negatively with triglyceride. CONCLUSION AND IMPLICATIONS: Alterations of trace elements may have a significant role in the pathogenesis of MetS and T2DM patients. It is suggested that the body status of copper, magnesium, and zinc might be significantly correlated with components of MetS in T2DM patients; and plasma copper levels may be correlated with complications of type 2 diabetes mellitus.

Oxidant/antioxidant status in Type-2 diabetes mellitus patients with metabolic syndrome.

BACKGROUND: The concurrence of metabolic syndrome (MS) and diabetes mellitus (DM) is increasing worldwide. The long-term complications of these chronic diseases are a threat to patients' well-being. Oxidative stress is involved in the pathogenesis of several diseases. To understand the basic pathophysiological mechanisms of Type-2 DM (T2DM) and its related complications, we aimed to investigate the oxidant/antioxidant status and Na+-K+ ATPase activity in T2DM with MS. MATERIALS AND METHODS: A population of ninety individuals including fifty patients diagnosed with T2DM and MS, but without overt diabetes complications, and forty individuals without T2DM or MS as control group participated in this study. Plasma malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, total antioxidant capacity (TAC), and Na+-K+ ATPase activity were assessed by standard laboratory methods. RESULTS: Plasma MDA in patients group was statistically significantly higher than that of controls (P ≤ 0.05). Whereas, Na+-K+ ATPase activity was statistically significantly lower in patient group (P ≤ 0.05). TAC, CAT, SOD, and GPx enzyme activities were not statistically significantly different between two groups (P > 0.05). Results from the patient group showed positive correlations between CAT activity and triglyceride and positive correlations between GPx activity and weight, body mass index (BMI), and waist circumference. In addition, there was a positive correlation between MDA results with high-density lipoprotein-cholesterol (HDL-C) and total cholesterol and a negative correlation with TAC, BMI, and weight (P ≤ 0.05) in controls. CONCLUSION: Because T2DM patients were without any vascular complications, antioxidant defense results may reflect the lack of progression of diabetes complications in these patients. These results emphasize the need for initial and continued assessment of cardiovascular disease risks in diabetic individuals. Implementation of timely interventions may improve the management of diabetes and prevent the progression of diabetes complications.

The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome.

BACKGROUND: Insulin resistance (IR) is associated with low-grade systemic inflammation. It plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic syndrome (MetS). It is unclear whether diabetic patients with MetS confer elevated CVD risk and outcomes beyond the impact of individual's components of MetS. The aim of this study is to highlight the central role of IR, inflammation, triglyceride/high-density lipoprotein- cholesterol (TG/HDL-C) ratio, and atherogenic index of plasma (AIP) in T2DM with MetS. MATERIALS AND METHODS: This cross-sectional study comprised 130 men distributed into three groups, namely Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were collected for the measurement of blood lipid profile, glucose, insulin, hemoglobin A1c, and high-sensitivity C-reactive protein (hs-CRP). TG/HDL-C ratio, AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS: Significant positive association was observed between HOMA-IR and hs-CRP only in Group II and between HOMA-IR and TG/HDL-C ratio in all subjects. Significant differences were seen in waist and hip circumferences, waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose, TGs, HDL-C, insulin, hs-CRP, HOMA-IR, TG/HDL ratio, and AIP between Controls and Group I with Group II. CONCLUSIONS: In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA-IR and TG/HDL-C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients.

Biochemical changes in blood of type 2 diabetes with and without metabolic syndrome and their association with metabolic syndrome components.

BACKGROUND: Multiple factors are involved in the development and progression of type 2 diabetes mellitus (DMII) to DMII with metabolic syndrome (MetS) and cardiovascular complications. To identify some of these factors, we aim to investigate the changes in erythrocyte membrane Na(+)/K(+)-ATPase activity, serum glucose, insulin, lipid profile, hemoglobin A1C (HbA1c), high-sensitivity C-reactive protein (hs-CRP), anthropometric measurements, and blood pressure in DMII with and without MetS. MATERIALS AND METHODS: This cross-sectional study comprised 155 male subjects distributed into three groups as healthy controls (50 non-DMII volunteers), Group I (50 DMII without MetS), and Group II (55 DMII with MetS). Fasting blood samples were taken for the measurement of glucose, insulin, HbA1c, hs-CRP and lipid profile. Na(+)/K(+)-ATPase activity was determined in erythrocyte ghost. RESULTS: Na(+)/K(+)-ATPase activity was significantly decreased in DMII groups compared with controls. No significant difference was shown in Na(+)/K(+)-ATPase activity between DMII groups. Total ATPase activity, total cholesterol and low-density lipoprotein-cholesterol levels were similar in the three groups. Levels of insulin, hs-CRP, triacylglycerols, systolic blood pressure, weight, waist and hip circumference, waist/hip ratio, and body mass index were significantly elevated and high-density lipoprotein-cholesterol significantly decreased only in Group II. Significant differences in serum glucose and hip circumference were seen between the groups. No significant differences in HbA1c levels were observed between DMII groups. CONCLUSION: Changes in many of the measured risk factors that occurred only in Group II compared with controls and Group I may provide an explanation of how DMII progresses to DMII with MetS and future cardiovascular complications.