Recent evidence suggests that blockade of the reninangiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocininduced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZinduced diabetic rats given vehicle or 20 mg ⅐ kg ؊1 ⅐ day ؊1 losartan for 8 weeks. Insulin and -adrenergic stimulation failed to increase the glucose uptake rate in STZ cardiomyocytes, whereas the ␣-adrenergic effect persisted. Concurrently, a typical prolongation of action potential duration (APD) and a decrease of transient outward current (I to ) were recorded in patchclamped STZ myocytes. Treatment with losartan did not affect body weight or glycemia of diabetic or control animals. However, in losartan-treated STZ-induced diabetic rats, -adrenergic؊mediated enhancement of glucose uptake was completely recovered. APD and I to were similar to those measured in losartan-treated control rats. A significant (P < 0.0001) correlation between metabolic and electrophysiological parameters was found in control, diabetic, and losartan-treated diabetic rats. Thus, angiotensin receptor blockade protects the heart from the development of cellular alterations typically associated with diabetes. These data suggest that angiotensin receptor blockers may represent a new therapeutic strategy for diabetic cardiomyopathy. Diabetes 53
Tecoma stans is a plant traditionally used in Mexico for the control of diabetes. Amongst the alkaloids isolated from the plant harvested in Egypt, Tecomine was shown to be one of the compounds responsible for the hypoglycemic action. Given the interest in substances able to treat type II diabetes, we isolated the main alkaloids present in the plant growing in Egypt and Brazil and tested them in vivo on db/db mice. Contrary to previous literature reports on different animal models, Tecomine was unable to modify glycemia; the only effect seen being a decrease in plasma cholesterol levels. On the contrary, when tested in vitro on glucose uptake in white adipocytes, the compound showed a marked effect. The two other alkaloids isolated, namely 5b-Hydroxyskitanthine, early called Base C, and Boschniakine were inactive both in vivo and in vitro assays.
1 In starved mice, the anorectic activity of methylamine (MET) and benzylamine (BZ), both substrates of semicarbazide-sensitive benzylamine oxidases (Bz-SSAO), was compared with that of the potassium channel blocking agents charybdotoxin (ChTX), tetraethylammonium (TEA), gliquidone (GLI), ammonium chloride ( 4 Antisense oligodeoxyribonucleotides (aODN) to Kv1.1 potassium channels abolished the e ect of BZ and TEA, but was ine ective in reducing the activity of MET and other compounds. 5 These results suggest that MET is endowed with peculiar hypophagic e ects at dosage levels that are not able to a ect gross behaviour in mice. The e ect of MET, di erently from BZ, seems unrelated to an increase in the central release of monoaminergic mediators, as well as to a Kv1.1 blocking activity. Through a reduction of the endogenous breakdown of MET, Bz-SSAO inhibitors enhance the central pharmacological activity of this amine.
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