Metformin, routinely used as first-line drug in the treatment of type 2 diabetes, has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways, which prevent the mPTP from opening and rupturing it and therefore, protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed. Given as a preconditioning and/or postconditioning agent, metformin has been shown to decrease infarct size and improve survival rates after myocardial infarction. Metformin has further been reported to restore depleted PGC-1α levels and improve mitochondrial biogenesis by increasing phosphorylation of eNOSser1177, which produces NO and leads to reduced vascular inflammation and myocardial injury after ischemia. There is strong evidence suggesting that metformin improves cardiovascular outcomes by influencing metabolic signal transduction pathways. There are growing calls for metformin use to be expanded off-label beyond the traditional glycemic control. We review experimental evidence for metformin's impact on cardiovascular disease and its underlying molecular mechanisms of action and also discuss why significant gains made in experimental conditions have not translated into significant therapeutic applications.
BackgroundHypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.ObjectivesTo investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.MethodsSprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively.ResultsStretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group.ConclusionsNaringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.
Our study first determined what juveniles know about the juvenile court process. Second, it evaluated a DVD designed to be a systematic and simple way to improve this knowledge. A pre- and posttest design was used with two pilot samples and two samples from the population of interest. A sample from a juvenile detention center (n = 118) was the focus of this study. Initial knowledge of the court process was quite low for the detention sample (pretest M = 64.0%, SD = 14.2%). All samples experienced a significant improvement of knowledge after watching the DVD. Youth in the detention sample had a mean improvement from pretest to posttest of 6.4% (SD = 11.9%), with mean scores at posttest being 70.3% (SD = 17.4%). Respondents varied in their performance on different question topics, scoring the lowest on questions related to what happens at juvenile court hearings. The social and demographic variables of age, race, gender, grades in school, number of previous arrests, and the number of times the respondent had been to court were evaluated through regression analysis. Age and race were found to be significantly related to pretest scores, and race was significantly related to improvement scores.
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