Diabetic hearts exhibit decreased responsiveness to stimulation by -adrenoreceptor (-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of -AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to  1 -AR agonist stimulation, but not to  2 -AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac  1 -,  2 -, and  3 -ARs and looked at whether these changes could be restored with insulin treatment. Using reverse transcription-polymerase chain reaction (RT-PCR), PAGE, and Western blot analysis, we found that  1 -AR mRNA and protein levels decreased by 34.9 ± 5.8 and 44.4 ± 5.8%, respectively, in 14 week-STZtreated diabetic rat hearts when compared with agematched controls. On the other hand, mRNA levels encoding  2 -and  3 -ARs increased by 72.5 ± 16.6 and 97.3 ± 26.1%, respectively. Although the latter translated into a proportional increase in  3 -AR protein levels (100.0 ± 17.0%),  2 -AR protein levels decreased to 82.6 ± 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored  1 -AR mRNA and protein levels to 60.1 ± 8.4 and 83.2 ± 5.0%, respectively, of control. Although insulin treatment minimally attenuated the rise in mRNA levels encoding  2 -and  3 -ARs, the steady-state levels of these proteins returned to near control values. These data suggest that the decreased responsiveness of diabetic hearts to stimulation of -AR agonists may be due to a decrease in  1 -AR and an increase  3 -AR expression. Diabetes 50: [455][456][457][458][459][460][461] 2001
Despite the significant developments in the treatment of diabetes mellitus, diabetic patients still continue to suffer from cardiac complications. The increase of cardiac adrenergic drive may ultimately contribute to the development and progression of diabetic cardiomyopathy. beta-Adrenoceptors play an important role in the regulation of heart function. However, responsiveness of diabetic heart to beta-adrenoceptor agonist stimulation is diminished. The chronotropic responses mediated by beta(1)-subtype, which is mainly responsible for cardiac effects of catecholamines are decreased in the atria of diabetic rats. The expression of cardiac beta(1)-subtype is significantly decreased in diabetic rats as well. beta(2)-Adrenoceptors also increase cardiac function. Although the expression of this subtype is slightly decreased in diabetic rat hearts, beta(2)-mediated chronotropic responses are preserved. On the other hand, functional beta(3)-adrenoceptor subtype was characterized in human heart. Interestingly, stimulation of cardiac beta(3)-adrenoceptors, on the contrary of beta(1)- and beta(2)-subtypes, mediates negative inotropic effect in human ventricular muscle. Cardiac beta(3)-adrenoceptors are upregulated in experimental diabetes as well as in human heart failure. These findings suggest that each beta-adrenoceptor subtype may play an important role in the pathophysiology of diabetes-induced heart disease. However, it is still not known whether the changes in the expression and/or responsiveness of beta-adrenoceptors are adaptive or maladaptive. Therefore, this review outlines the potential roles of these receptor subtypes in cardiac pathologies of diabetes.
In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Various types of diabetic complications affecting different systems in the body have been reported. The clinical course of the disease is largely determined by those complications. Therefore, an important area is obviously prevention or treatment of the disabling complications associated with diabetes. Recent investigations address to the problem from different angles, since the development of diabetes-induced long-term problems is likely a multifactorial process. In this review, some of the factors which are implicated in the development of these complications such as neuropathy, retinopathy and cataract are discussed. Some of the approaches which have been used in attempts to prevent or delay those abnormalities are reported as well.
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