Histochemical studies on the conduction system of diabetic rat hearts.

Abstract

Summary. We studied the metabolism of the conduction system and the working myocardium in diabetic rat hearts by enzyme histochemistry. The experiment was performed three weeks following the administration of streptozotocin (65 mg/kg) to male Wistar rats. The hearts were quickly excised and tissue was frozen immediately by immersion in isopentane at -30C and cut into 16 pm thick sections in a cryostat. The PAS positive reaction was increased in the conduction system compared to the working myocardium in control rats. In diabetic rat hearts, these reactions in the working myocardium and the conduction system were strongly increased compared to control hearts. Several enzyme activities, such as phosphofructokinase, pyruvate dehydrogenase, glucose-6-phosphate dehydrogenase, Na-K ATPase, were reduced in both the working myocardium and conduction system of diabetic rat hearts. These results suggest that the changes in metabolic condition also exist in the conduction system of the diabetic rat hearts as well as the working myocardium.Diabetic hearts are known to have an altered myocardial metabolism, both in man and experimental animals (MCDANIEL et al., 1988). Myocardial metabolism in the poorly controlled diabetic animal is characterized by the exclusive oxidation of fatty acids and ketone bodies, and a low rate of glucose utilization (TAEGTMEYER and PASSMORE, 1985). The conduction system has been reported to have different metabolic properties compared to the working myocardium in normal hearts (SOGABE et al., 1987). It is well known that not only myocardial contractility but also the heart rate is reduced in diabetic animals. Alterations in the working myocardial metabolism have been extensively investigated by biochemical and enzyme histochemical methods in diabetic animals (TARACH,1978), however, there has been no systematic study of the myocardial metabolism of the conduction system in diabetic animals. The present study was therefore undertaken to investigate alterations in the energy metabolism of the conduction system in diabetic rats. The cardiac conduction system is not easily isolated by dissection, and it is difficult to obtain a sufficient amount of material for accurate biochemical studies. For this reason, we used enzyme histochemistry and studied the activities of some enzymes related to glucose metabolism in diabetic rat hearts. MATERIALS AND METHODS Animals and tissue preparationMale Wistar rats weighing approximately 150 g were randomly separated into control and diabetic groups. Diabetic groups received an intravenous injection of 0.1 M citrate-buffered streptozotocin (Sigma Chemical Co.) at a dosage of 65 mg/kg body weight (GANDA et al., 1976). Control animals received a similar injection of citrate-buffer alone. These animals were kept for three weeks under normal laboratory conditions with access to water and rat chow ad libitum and then killed by decapitation at AM 9: 00-11: 00 after overnight fasting. Post-fasting blood glucose levels were measured by the glucose oxidase method, and a blood...

Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex

“…Experiments in which the cortices were separated into glomerular and tubular fractions showed that both glomeruli and tubules displayed decreased G6PD activity in diabetic animals compared with NDM controls (data not shown). This observation is consistent with previously published data in which decreased G6PD activity has also been observed in liver (33), aorta (43), heart (27,42), and Leydig cells (5) from diabetic animal models. Moreover, it has been reported that patients with diabetes have decreased G6PD levels in liver (6), mononuclear leukocytes (34,44), and erythrocytes (9,10).…”

Increasing Glucose 6-Phosphate Dehydrogenase Activity Restores Redox Balance in Vascular Endothelial Cells Exposed to High Glucose

“…For example in cell culture models of endothelial cells and mesangial cells, G6PD is significantly inhibited by high glucose [27]. In animal models, decreased G6PD activity has been reported in liver [28], aorta [29], heart [30], [31], and Leydig cells [32]. In diabetic patients, decreased G6PD activity has been detected in percutaneous liver biopsies [32], mononuclear leukocytes [33], [34], and erythrocytes [35], [36].…”