Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus, characterized by peripheral insulin resistance, is a major lifestyle disorder of the 21^stCentury. Raw garlic homogenate has been reported to reduce plasma glucose levels in animal models of type 1 diabetes mellitus. However, no specific studies have been conducted to evaluate the effect of raw garlic on insulin resistance or type 2 diabetes mellitus. This study was designed to investigate the effect of raw garlic on fructose induced insulin resistance, associated metabolic syndrome and oxidative stress in diabetic rats.</p> <p>Methods</p> <p>Male Sprague Dawley rats weighing 200-250 gm body weight were divided into 3 groups (n = 7 per group) and fed diet containing 65% cornstarch (Control group) and 65% fructose (Diabetic group) for 8 weeks. The third group (Dia+Garl group) was fed both 65% fructose and raw garlic homogenate (250 mg/kg/day) for 8 weeks. Whole garlic cloves were homogenized with water to make a fresh paste each day.</p> <p>Results</p> <p>At the end of 8 weeks, serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance, as measured by glucose tolerance test, were significantly (p < 0.01) increased in fructose fed rats (Diabetic group) when compared to the cornstarch fed (Control) rats. Administration of raw garlic to fructose fed rats (Dia+Garl group) significantly (p < 0.05) reduced serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance when compared with fructose fed rats. Garlic also normalised the increased serum levels of nitric oxide (NO) and decreased levels of hydrogen sulphide (H₂S) after fructose feeding. Although body weight gain and serum glycated haemoglobin levels of fructose fed rats (Diabetic group) were not significantly different from control rats, significant (p < 0.05) reduction of these parameters was observed in fructose fed rats after garlic administration (Dia+Garl group). Significant (p < 0.05) increase in TBARS and decrease in GSH was observed in diabetic liver. Catalase was not significantly affected in any of the groups. Administration of raw garlic homogenate normalised both hepatic TBARS and GSH levels.</p> <p>Conclusions</p> <p>Our study demonstrates that raw garlic homogenate is effective in improving insulin sensitivity while attenuating metabolic syndrome and oxidative stress in fructose-fed rats.</p

SIRT-3 Modulation by Resveratrol Improves Mitochondrial Oxidative Phosphorylation in Diabetic Heart through Deacetylation of TFAM

Background and Purpose: Mitochondrial dysfunction remains the crucial cause for many heart diseases including diabetic cardiomyopathy (DCM). Sirtuin-3 (SIRT-3) is a protein deacetylase localized in the mitochondria and regulates mitochondrial function. Being a noteworthy mitochondrial protein deacetylase enzyme, the role of SIRT-3 in DCM is yet to be explored. Experimental Approach: Diabetes mellitus (Type-I, T1DM) was induced using streptozotocin (STZ, 50 mg/kg) in male Sprague Dawley (SD) rats. Rats with &gt;200 mg/dL blood glucose levels were then divided randomly into two groups, DIA and DIA + RESV, where vehicle and resveratrol (25 mg/kg/day) were administered orally in both groups, respectively. Cardiac oxidative stress, fibrosis, and mitochondrial parameters were evaluated. H9c2 cells were transfected with SIRT-3 siRNA and shRNA, and ORF plasmid for silencing and overexpression, respectively. Key Results: After eight weeks, diabetic rat heart showed reduced cardiac cell size, increased oxidative stress and reduction of the activities of enzymes involved in mitochondrial oxidative phosphorylation (OXPHOS). There was reduced expression and activity of SIRT-3 and mitochondrial transcription factor (TFAM) in diabetic heart. Reduced SIRT-3 expression is also correlated with increased acetylation, decreased mitochondrial DNA (mtDNA) binding activity of TFAM, and reduced transcription of mitochondrial DNA encoded genes. Administration of resveratrol prevented the decrease in SIRT-3 and TFAM activity, which was corresponding to the reduced acetylation status of TFAM. Silencing SIRT-3 using siRNA in H9C2 cells showed increased acetylation of TFAM. Conclusion and Implications: Together our data shows that resveratrol activates SIRT-3, regulates the acetylation status of TFAM and preserves the mitochondrial function along with cellular size in diabetic rat heart

Hyperglycaemia Enhances Nitric Oxide Production in Diabetes: A Study from South Indian Patients - Fig 3

<p>A. NO levels produced from HUVEC cells after 4hrs treatment of D-Glucose (10,50mM). Data were represented as ± SEM. * p<0.05, ** p<0.01 vs Control (CT). B. NO levels produced from HUVEC cells after 8hrs treatment of D-Glucose (10,50mM). Data were represented as mean ± SEM. * p<0.05, ** p<0.01, *** p< 0.001 vs Control (CT).</p

Clinical and biochemical characteristics of the study subjects.

<p>Results are expressed as Median (interquartile range).</p><p>^acomparison between CT and T2DM,</p><p>^bcomparison between CT and DMHT,</p><p>^dcomparison between CT and DMCD,</p><p>^ecomparison between T2DM and DMHT,</p><p>^fcomparison between T2DM and CAD,</p><p>^hcomparison between DMHT and CAD,</p><p>ⁱcomparison between DMHT and DMCD,</p><p>^jcomparison between CAD and DMCD.</p><p>*p<0.05,</p><p>**p<0.01,</p><p>***p<0.001. NS-No significance.</p><p>Clinical and biochemical characteristics of the study subjects.</p

Sequence of primers used for real-time PCR.

<p>Sequence of primers used for real-time PCR.</p

Serum nitric oxide levels in human subjects.

<p>A. Human serum NO levels in Control (CT) and Type 2 diabetes (T2DM). Data were represented as box (median (IQR)) and whisker plots. *** p<0.001 vs Control (CT). B. Human serum NO levels in Control (CT), Coronary artery disease (CAD) and Type 2 diabetes with coronary artery disease (DMCD). Data were represented as box (median (IQR)) and whisker plots. *** p<0.001 vs Control (CT), ^###p<0.001 vs CAD. C. Human serum NO levels in Control (CT) and Type 2 diabetes with hypertension (DMHT). Data were represented as box (median (IQR)) and whisker plots. D. Human serum NO levels in two group of patients having diabetic duration below 5 years and above 5 years. Data were represented as box (median (IQR)) and whisker plots. ***p<0.001 vs diabetic duration below 5 years.</p