OBJECTIVE: In diabetes, intracellular accumulation of sorbitol resulting from the high extracellular levels of glucose leads to depletion of intracellular compounds including taurine. This is associated with the development of late diabetic complications such as cardiomyopathy. The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine. However, the interaction between taurine, angiotensin II type2 receptor (AT2) and cardiomyopathy related to angiotensin II is still unknown. This study investigates the roles of taurine and AT2 in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy. METHODS: Of 60 female 4-week-old Wistar rats, 8 were treated with common diet and the other 52 with high sugar/fat diet (during the whole experiment) to induce insulin resistance. At the 4th week, of the 52 rats, 7 treated with sodium citrate buffer (pH = 4.5) were grouped into control group1 (con1) and the other 45 were treated by intraperitoneal injection (I.P) with STZ to develop type 2 diabetes. At the 28th week, the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation (-dp/dt(max)) was detected by a cannula through right carotid artery. After the cannula operation, of the 45 rats, all the living 24 with -dp/dt(max)< or = 5250 mmHg/s, who had developed diabetic cardiomyopathy, were grouped as follows: 7 treated with double distilled H2O (I.P) were grouped into control group2 (con2). 8 treated with AT2 agonist (CGP42112A) (I.P) were grouped into experimental group1 (exp1). Another 9 treated with taurine (I.P) were grouped into experimental group2 (exp2). All injections lasted 4 weeks (Q.D) and the heart weight (HW) was recorded. To examine cardiomyocyte apoptosis index (CAI), mRNA and protein of AT2 and Bcl-2 in cardiomyocytes, methods of terminal-deoxynucltidyl transferase mediated nick end labeling (TUNEL), reversal transcription polymerase chain reaction (RT-PCR) and immunoblot (Western Blot) were used, respectively. RESULTS: Values of -dp/dt(max) in exp1, exp2 or con2 were much less than those in con1, respectively (p < 0.01). CAI (= stained cell number/total cell number x 100%) and AT2 values both in mRNA and protein levels in con1 were less than those in the other three groups, respectively (p < 0.01). The three parameters above were more in exp1 but less in exp2 than those in con2, respectively (p < 0.01). The three parameters and HW in exp1 were much higher than those in exp2, respectively (p < 0.01). Changes of Bcl-2 were opposed to those of AT2. CONCLUSIONS: A high expression of AT2 may accelerate the apoptosis of cardiomyocytes in diabetic rats and play a role in precipitating diabetic cardiomyopathy; taurine may protect diabetic rats from developing cardiomyopathy also by downregulating AT2 receptors.
OBJECTIVE: In diabetes, intracellular accumulation of sorbitol resulting from the high extracellular levels of glucose leads to depletion of intracellular compounds including taurine. This is associated with the development of late diabetic complications such as cardiomyopathy. The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine. However, the interaction between taurine, angiotensin II type2 receptor (AT2) and cardiomyopathy related to angiotensin II is still unknown. This study investigates the roles of taurine and AT2 in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy. METHODS: Of 60 female 4-week-old Wistar rats, 8 were treated with common diet and the other 52 with high sugar/fat diet (during the whole experiment) to induce insulin resistance. At the 4th week, of the 52 rats, 7 treated with sodium citrate buffer (pH = 4.5) were grouped into control group1 (con1) and the other 45 were treated by intraperitoneal injection (I.P) with STZ to develop type 2 diabetes. At the 28th week, the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation (-dp/dt(max)) was detected by a cannula through right carotid artery. After the cannula operation, of the 45 rats, all the living 24 with -dp/dt(max)< or = 5250 mmHg/s, who had developed diabetic cardiomyopathy, were grouped as follows: 7 treated with double distilled H2O (I.P) were grouped into control group2 (con2). 8 treated with AT2 agonist (CGP42112A) (I.P) were grouped into experimental group1 (exp1). Another 9 treated with taurine (I.P) were grouped into experimental group2 (exp2). All injections lasted 4 weeks (Q.D) and the heart weight (HW) was recorded. To examine cardiomyocyte apoptosis index (CAI), mRNA and protein of AT2 and Bcl-2 in cardiomyocytes, methods of terminal-deoxynucltidyl transferase mediated nick end labeling (TUNEL), reversal transcription polymerase chain reaction (RT-PCR) and immunoblot (Western Blot) were used, respectively. RESULTS: Values of -dp/dt(max) in exp1, exp2 or con2 were much less than those in con1, respectively (p < 0.01). CAI (= stained cell number/total cell number x 100%) and AT2 values both in mRNA and protein levels in con1 were less than those in the other three groups, respectively (p < 0.01). The three parameters above were more in exp1 but less in exp2 than those in con2, respectively (p < 0.01). The three parameters and HW in exp1 were much higher than those in exp2, respectively (p < 0.01). Changes of Bcl-2 were opposed to those of AT2. CONCLUSIONS: A high expression of AT2 may accelerate the apoptosis of cardiomyocytes in diabeticrats and play a role in precipitating diabetic cardiomyopathy; taurine may protect diabeticrats from developing cardiomyopathy also by downregulating AT2 receptors.
Authors: Ranjan Banerjee; Jun He; Carolyn Spaniel; Megan T Quintana; Zhongjing Wang; James Bain; Christopher B Newgard; Michael J Muehlbauer; Monte S Willis Journal: Metabolomics Date: 2014-07-14 Impact factor: 4.290