Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Streptozotocin-induced diabetes produced significant changes on the drug metabolizing enzyme machinery of rat kidney microsomes. 2. It reduced the cytochrome P-450 content by 30%, this effect being reversed by insulin therapy. 3. Total androstenedione oxidative metabolism was increased 2.5-fold and insulin treatment partially antagonized this activation. 4. Total testosterone hydroxylase activities were not modified by diabetes nor by insulin but the formation of 2 alpha OH testosterone and 6 beta OH testosterone were distinct in diabetes or insulin treated diabetic rats. 5. Only UDP-glucuronyltransferase activity for PNP was found in kidney microsomes. Diabetes determined a lower UDPGT substrate efficiency not reversed by insulin therapy.
Gen Pharmacol 1995 Jan
PMID:Kidney drug metabolizing activities in streptozotocin diabetic rats. 771 53

1. The effect of glyburide treatment on glutathione peroxidase activity and glutathione levels of non-insulin diabetic rats has been studied. 2. Hepatic glutathione and glutathione peroxidase concentrations were significantly reduced in diabetic animals. 3. Glyburide treatment of diabetic rats for 4 weeks corrected the changes on the glutathione levels observed in diabetic liver. 4. High blood glucose levels of untreated diabetic rats were decreased following glyburide treatment as well. 5. Administration of glyburide to diabetic rats reversed the diabetes-induced changes suggesting that glyburide may directly increase liver glutathione concentrations.
Gen Pharmacol 1994 Sep
PMID:Effect of the sulfonylurea glyburide on glutathione and glutathione peroxidase activity in alloxan-induced diabetic rat hepatocytes. 783 30

1. Insulin-like effects of vanadium compounds have been reported in various experimental conditions. Effects of vanadate on the decreased beta-adrenergic responsiveness of the rat duodenum due to streptozotocin diabetes were investigated to determine its influence on diabetic gastro-intestinal complications as well as its effects on the carbohydrate metabolism. 2. Administration of sodium orthovanadate to streptozoticin-diabetic rats in drinking water (0.7 mg/ml) for 4 weeks resulted in an improvement of carbohydrate metabolism noticed by increased serum levels of insulin and decreased blood levels of glucose as reported in previous studies. 3. Vanadate treatment of streptozotocin-diabetic rats also corrected the diabetic changes in the beta-adrenergic responsiveness of the rat duodenum to salbutamol suggesting a beneficial effect on the diabetic complications of rat gastro-intestinal tract. The same treatment with vanadate did not cause any alteration in the beta-adrenergic responsiveness of isolated duodenum from non-diabetic rats. 4. From the findings obtained, it is concluded that vanadate possesses an insulin-like effect on the beta-adrenergic responsiveness of the rat gastro-intestinal tract. Since vanadate treatment did not alter the beta-adrenergic responses of isolated duodenum from non-diabetic rats it seems likely that the insulin-like effect of vanadate is dependent on increased responsiveness of the gastrointestinal tract to circulating insulin.
Gen Pharmacol 1994 Oct
PMID:Vanadate treatment reverses gastrointestinal complications in the streptozotocin-diabetic rats. 787 32

1. Plasma endothelin-1 level as well as plasma lipid and glucose levels was markedly elevated in the rats treated with streptozotocin 8 weeks earlier. 2. Positive inotropic response, which was significantly greater than that in the age-matched control, was produced by endothelin-1 in the left atria isolated from diabetic rats. On the other hand, the contractile response of thoracic aorta to endothelin-1 was conversely attenuated in the diabetic rats. Such contrasting effects of diabetes between the atrial and aortic muscles were observed in the responsiveness to other contractile drugs. Endothelium-dependent relaxation in the thoracic aorta was also significantly attenuated in diabetic rats. However, the basal twitch contraction of left atria, the chronotropic responses to endothelin-1, isoproterenol and carbachol and the relaxation of the aorta by papaverine were not affected by diabetes. 3. These results suggest that the contractile responsiveness of atrial and aortic muscles and the endothelial functions significantly alter during diabetes for 8 weeks.
Gen Pharmacol 1994 Oct
PMID:Effects of chronic diabetes on the responsiveness to endothelin-1 and other agents of rat atria and thoracic aorta. 787 48

1. Decreased beta-adrenergic responses have been reported in gastro-intestinal tract of rats with diabetes mellitus. Effects of glyburide and insulin on the decreased beta-adrenergic responsiveness of the gastro-intestinal tract due to non-insulin-dependent diabetes were investigated using duodenum, jejunum and ileum from rats which were injected with alloxan in their neonatal periods. 2. Insulin treatment of non-insulin-dependent diabetic rats for 10 days corrected the decreased beta-adrenergic responses of the isolated duodenum, jejunum and ileum confirming the previous results obtained from insulin-dependent diabetic rats. 3. Glyburide treatment alone for 3 weeks also reversed the changes in the gastro-intestinal beta-adrenergic responses of non-insulin-dependent diabetic rats. Combination of glyburide with insulin, however, did not cause an additive or supra-additive interaction in terms of beta-adrenergic sensitivities of the diabetic tissues. 4. The results obtained in the present study strongly suggested that non-insulin-dependent diabetes may cause a decrease in the number of gastro-intestinal beta-adrenoceptors, while glyburide and insulin treatments correct the changes related to beta-adrenoceptors. The effect of insulin on the beta-adrenergic sensitivity of diabetic rat duodenum, jejunum and ileum may occur via a direct mechanism, whereas glyburide seems to be effective on the beta-adrenergic responses through the increases in the insulin secretion and/or in the number of gastro-intestinal insulin receptors.
Gen Pharmacol 1994 Nov
PMID:The effects of glyburide and insulin on the decreased beta-adrenergic responsiveness of the gastrointestinal tract in rats with non-insulin-dependent diabetes. 789 68

1. Functional and morphological abnormalities in vas deferens have been reported by both experimental and clinical studies as a cause of genital function abnormalities in diabetic males. 2. In the present study, contractile effects of noradrenaline and tyramine in isolated vas deferens from rats with short- and long-term alloxan diabetes were investigated by comparing with those from control rats. For this purpose, intrinsic activities (alpha E value) and apparent affinity constants (pD2 value) for contractile effects of noradrenaline and tyramine in the isolated rat vas deferens were calculated in normal rats and rats with short- and long-term alloxan diabetes. 3. Apparent affinity constants for contractile effects of noradrenaline in the isolated rat vas deferens were increased depending on both short- and long-term alloxan diabetes. By contrast, apparent affinity constants for contractile effects of tyramine in the isolated rat vas deferens were attenuated due to both short- and long-term alloxan diabetes. Intrinsic activities for both noradrenaline- and tyramine-induced contractions of rat vas deferens, however, were increased due to short-term diabetes and decreased due to long-term diabetes. 4. Experimental findings obtained in this study indicate that vas deferens preparations from rats with short- and long-term alloxan-induced diabetes exhibit altered alpha-adrenergic responsiveness depending on time elapsed. While short-term alloxan diabetes causes enhanced alpha-adrenergic responses in the rat vas deferens, the long-term diabetes decreases the responses in this tissue.
Gen Pharmacol 1994 Nov
PMID:Altered alpha-adrenergic responses of vas deferens to noradrenaline and tyramine from rats with short- and long-term alloxan diabetes. 789 69

1. Experimental models of diabetes are increasingly used for the investigation of cardiovascular complications as well as other complications due to diabetes mellitus. However, animal models have been used in relatively few studies on the myocardial alpha 1-adrenergic responses. Hence, this report describes the effect of alloxan-induced diabetes and insulin-treatment on the alpha 1-adrenergic responses of the isolated rat atria. 2. Alloxan-induced diabetes caused an increase in the alpha 1-adrenergic responses assessed in isolated spontaneously beating rat atria. Both pD2 and alpha E values for phenylephrine, an alpha 1-adrenergic agonist were increased in atria from rats with alloxan diabetes. 3. Insulin treatment (4 IU/kg/day, s.c.) for 10 days normalized the changes in diabetic rat atria. pD2 and alpha E values for phenylephrine were slightly lower than those from control rats. Serum levels of thyroid hormones returned to normal following insulin treatment as well. 4. The effect of insulin on the increased alpha 1-adrenergic responses of rat atria due to alloxan diabetes seems to be related to thyroid hormone metabolism, since thyroidectomy also changed the atrial parameters measured. 5. The finding obtained in this study suggest that experimentally-induced diabetes increases alpha 1-adrenergic sensitivity of the rat atria possibly due to an increased receptor affinity, but these changes can be reversed with insulin treatment.
Gen Pharmacol 1994 May
PMID:Increased alpha 1-adrenergic responsiveness of alloxan diabetic rat atria: effects of insulin therapy and thyroidectomy. 792 5

1. A 6-week gliclazide treatment improved left ventricular developed pressure and left ventricular end-diastolic pressure, left ventricular pressure-rate products in isolated working hearts from streptozotocin-induced diabetic rats. 2. Post-ischemic recovery in heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, left ventricular pressure-rate products and cardiac work were also shown in gliclazide-treated diabetic rats. 3. Gliclazide treatment did not modify the degree of insulinopenia and hyperglycemia, nor the myocardial energy metabolism during ischemia-reperfusion. 4. The results suggest that the gliclazide treatment has a cardioprotective effect on basal and post-ischemic cardiac functions of chronic diabetes.
Gen Pharmacol 1994 Jul
PMID:Chronic gliclazide treatment affects basal and post-ischemic cardiac function in diabetic rats. 795 31

1. The role of the endothelium on the constrictor effect of noradrenaline (NA), and endothelium-dependent and endothelium-independent vasodilator effects of different agonists were determined in rings of aortae obtained from nondiabetic (control), non-insulin-dependent (NID-) diabetic and NID-diabetic rats treated with insulin. 2. The NA-induced contractions are markedly increased with no change in agonist potency (pD2 value) in aortae with intact endothelium obtained from NID-diabetic rats when compared to those from age-matched controls. Mechanical removal of the endothelium resulted in a significant increase in maximum contractile response of control aortae but not NID-diabetic aortae to NA relative to presence of endothelium. No significant difference was observed between the contractile responses of NID-diabetic and control aortae to NA after the removal of endothelium. 3. Endothelium-dependent relaxations elicited by acetylcholine (ACh), histamine, ATP and insulin strongly depressed in NID-diabetic aortae but the relaxations stimulated by sodium nitroprusside (SNP) did not change when compared to corresponding controls. There was no significant changes in the pD2 values calculated by agonist-induced relaxations of aortae from either untreated or insulin-treated NID-diabetic rats compared with controls. 4. NID-diabetes-induced alterations on the reactivity of aortae were significantly restored by in vivo insulin treatment. 5. These data indicate that impaired endothelium-dependent vasodilatory responses of aortae from NID-diabetic rats results in increased NA-induced contractions. It is possible that, impaired endothelium-dependent vasodilatory modulation of vasoconstriction may play a important role in development of vasospasm and hypertension in NID-diabetics.
Gen Pharmacol 1994 Jul
PMID:The role of the endothelium on enhanced contractile response of non-insulin-dependent diabetic rat aortae: effects of insulin treatment. 795 44

1. In this study, the maximal contractile responses to noradrenaline (NA) were significantly increased but pD2 values (sensitivity) were not significantly altered in aortas with endothelium from insulin-dependent (ID)-diabetic rats when compared to their controls. 2. Removal of the endothelium resulted in a significant increase in the maximum response of control and ID-diabetic aortas and also loss of the difference in maximum contractile response to NA between ID-diabetic aortas and their corresponding controls. 3. Endothelium-dependent relaxation stimulated by acetylcholine (ACh), methacholine, histamine, ATP and insulin, in aortic rings precontracted with NA were significantly attenuated but unchanged by A23187 in ID-diabetic vessels relative to controls. 4. Relaxations produced by sodium nitroprusside (SNP) in ID-diabetic aortas were similar to those in control vessels. 5. The sensitivity of ID-diabetic aortas to relaxant substances were not changed when compared with controls. 6. These results demonstrate that ID-diabetes-induced specific changes in vascular reactivity and endothelial cells have an important role on the maintenance of vascular tonus. This feature may be responsible for the major complications of diabetes such as macroangiopathy, vasospasm and high blood pressure in late stage of the disease.
Gen Pharmacol 1993 May
PMID:The role of endothelial cells on the alterations in vascular reactivity induced by insulin-dependent diabetes mellitus: effects of insulin treatment. 836 55


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