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)

To determine the vasodilative and negative inotropic effects of adenosine in hearts of diabetic rats, isolated hearts, perfused at constant perfusion pressure (Langendorff technique), were prepared from age-matched control Wistar rats and rats made diabetic 10 weeks prior to study by a single injection of streptozotocin (65 mg.kg-1, i.p.). Adenosine and nitroprusside each increased coronary inflow when administered either as bolus injections or as infusions. Coronary flow responses to nitroprusside were unchanged in diabetic hearts. Coronary flow responses of diabetic hearts to adenosine injections were unchanged, but responses to adenosine infusions tended to be larger than in normal hearts. Diabetes had no significant effect on the EC50 for either vasodilator. Adenosine inhibited the inotropic effect of isoproterenol (enhanced left ventricular (LV) pressure (P) and LV dP/dtmax) in normal hearts, independently of its vasodilative action. This negative inotropic action of adenosine appeared equally strong in diabetic hearts. We conclude that adenosine's coronary vasodilative and anti-beta-adrenergic, negative inotropic effects in the rat heart were not diminished after 10 weeks of streptozotocin-induced diabetes mellitus. Thus, earlier reports of diminished adenosine dilative efficacy in experimental diabetes may have been unique to those particular models.
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PMID:Vasodilative and anti-adrenergic effects of adenosine in diabetic rat hearts. 131 17

Sammo plant which is traditionally used in Egypt for the treatment of diabetes mellitus, was administered at low and high levels (4% and 8% respectively at the expense of starch) to adult male alloxanized albino rats, to study its effect on energy metabolism. Adenosine-5-triphosphate (ATP) in the brain (B), liver (L) and kidneys (K) organs of alloxanized rats was significantly lowered compared with the negative control. On the other hand, adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) contents in the same organs were elevated markedly. In this connection myokinase activity in cytoplasmic and mitochondrial fractions of B, L and K organs was stimulated at control. Also, the activities of some fundamental enzymes of the oxidative pentose phosphate pathway i.e. glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phospho-gluconate dehydrogenase (6-PGD) in cytoplasmic and mitochondrial fractions of the same organs were markedly increased. Administration of Sammo at low and high levels reduced the consumption of ATP in B, L and K organs relative to positive control. Whereas, ADP and AMP contents were relatively reduced. Also, myokinase activity in the same organs were relatively inhibited. The activity of G-6-PD and 6-PGD in cytoplasmic and mitochondrial fractions of the same organs were also decreased relative to the positive control.
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PMID:The effect of sammo administration on some fundamental enzymes of pentose phosphate pathway and energy metabolites of alloxanized rats. 157 54

Adenosine and prostaglandins of the E series inhibit lipolysis in adipocytes by binding to cell surface receptors. This inhibition is mediated via Gi. It has been reported that Gi is almost absent in livers from diabetic rats. Therefore, we have evaluated the sensitivity of adipocytes from diabetic rats to the adenosine analogue N6-phenylisopropyl adenosine (PIA) and to prostaglandin E1 (PGE1). Diabetes was induced with streptozocin (65 mg/kg i.v.), and after 7 days, adipocytes were isolated. Lipolysis (measured in the presence of adenosine deaminase) was inhibited by PIA and PGE1 in both control and diabetic cells. However, the dose-response curves were markedly shifted to the right in the cells from diabetic rats. The IC50 for PIA was 0.30 +/- 0.02 nM in controls and 0.83 +/- 0.08 in diabetic rats (P less than 0.001), and the IC50 for PGE1 was 3.16 +/- 0.18 nM in controls and 5.26 +/- 0.57 nM in diabetic rats (P less than 0.02). These findings indicate decreased sensitivity to both adenosine and PGE1. Adipocyte membranes were isolated from control and diabetic rats. Adenosine receptors (measured by binding of 125I-labeled hydroxy-PIA) were not altered in cells from diabetic rats. However, the ability of Gpp(NH)p (a nonhydrolyzable GTP analogue) to inhibit adenosine-receptor binding was markedly decreased in membranes from diabetic rats, suggesting a change at the level of Gi. The alpha-subunits of Gi1, Gi2, Gi3, and Gs were quantitated on Western blots with a series of recently characterized anti-peptide antisera. This revealed that the amounts of each of these G proteins were normal in membranes from the diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jan
PMID:Evidence for impaired coupling of receptors to Gi protein in adipocytes from streptozocin-induced diabetic rats. 184 51

1. The present study examined the reactivity of atria from control and spontaneously diabetic rats to various adrenoceptor agonists and to adenosine. 2. Isoprenaline (1.5 nM-1500 nM) produced concentration-dependent increases in inotropy which were unchanged in diabetic atria. However, the sensitivity to isoprenaline-induced changes in chronotropy was reduced in diabetic preparations. 3. In the presence of propranolol (2 microM), phenylephrine (0.2 microM-100 microM) produced concentration-dependent increases in both inotropy and chronotropy; however, atria from diabetic rats exhibited a much greater maximal response. The diabetic state did not alter the sensitivity to phenylephrine. 4. Adenosine (0.15 microM-300 microM) produced concentration-dependent decreases in both inotropy and chronotropy which were unchanged in diabetic atria. 5. Radioligand binding studies revealed that both alpha 1- and beta-adrenoceptor populations were substantially reduced in atria from diabetic rats. However, there was no change in receptor affinity for either adrenoceptor. 6. These results show that diabetes leads to an alteration in atrial reactivity to adrenoceptor stimulation. Future studies examining steps following hormone-receptor coupling are required in order to characterize this defect.
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PMID:Alterations in atrial reactivity in a strain of spontaneously diabetic rats. 257 82

We have previously found that the coronary dilator response to infused adenosine is attenuated in diabetic (alloxan) lambs. Adenosine responsiveness is restored by administration of insulin. The present studies tested the hypothesis that coronary flow changes with hypoxia, if mediated by adenosine, would also be modified. Studies were carried out in eight control and six diabetic lambs. The animals were anesthetized and prepared to maintain constant arterial pressure (reservoir), cardiac output (pump), and heart rate (paced). Atropine and practolol were given. Forced inspired oxygen was reduced in steps. Arterial and coronary sinus blood samples were analyzed for Po2, oxygen content, pH, hematocrit, and glucose. Myocardial oxygen delivery and uptake (MVO2) were calculated. Coronary flow increased identically in both control and diabetic animals as PaO2 was reduced below 60 Torr. Oxygen delivery and MVO2 fell equally in both groups. Acidosis potentiated hypoxic coronary flow changes. Alpha blockade (phentolamine) was without effect in control lambs but caused coronary flow to increase in diabetic lambs. Changes in coronary flow with hypoxia were unaffected, however. Insulin caused no change in the coronary dilator response to hypoxia in either control or diabetic lambs. It is concluded that coronary alpha tone is increased in diabetes but does not modify changes in coronary flow during hypoxia. As coronary flow responses to hypoxia were unaltered in diabetic lambs, and unaffected by insulin, adenosine may not be the primary mediator of coronary vascular dilatation. Potentiation of adenosine by tissue acidosis is apparently insufficient to explain these findings. The mechanism for coronary dilatation during hypoxia is unclear but may involve direct effects of reduced oxygenation of coronary vascular smooth muscle.
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PMID:Coronary vascular responses to hypoxia in the diabetic lamb: independence from adenosine and autonomic mechanisms. 301 81

We have recently shown that the coronary dilator action of adenosine is reduced in animals with experimental diabetes mellitus. Effects of insulin replacement are reported in the present study. Lambs, age 6-17 days, were studied 1-2 days after induction of diabetes with alloxan (150 mg/kg; n = 6). These were compared with nondiabetic controls, age 4-15 days (n = 5). A third group was studied after 8-15 days of diabetes (n = 3). In the acute diabetics blood glucose was 362 +/- 48 mg/dl. Heart rate, dP/dtmax, and myocardial O2 consumption did not differ from controls, but pH tended to be lower (7.29 +/- 0.03). Adenosine was given by left ventricular infusion. Coronary flow changes were significantly lower at all infusion rates (3-15 micrograms X min-1 X kg-1) in the untreated diabetics. Dose-response curves before and after insulin (10 U/kg) were identical in controls. However, in the diabetics, insulin enhanced the dilator response to adenosine, and changes in coronary flow at each infusion rate did not differ from controls. Aminophylline (6 mg/kg) abolished or sharply reduced the dilator responses to adenosine in both controls and diabetics (P less than 0.01). Animals diabetic 1-2 wk were unresponsive to adenosine. But after insulin, the nucleoside elicited vigorous coronary dilatation. It is concluded that insulinopenic diabetes is accompanied by sharply reduced adenosine sensitivity of coronary resistance vessels. Sensitivity is restored by giving insulin. This hormone may modulate adenosine receptor properties of vascular smooth muscle.
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PMID:Restoration of coronary dilator action of adenosine in experimental diabetes. 389 60

The effect of insulin on glucose transport (2-deoxyglucose uptake) in adipocytes was measured in the absence and in the presence of 10 mM sodium-DL-beta-hydroxybutyrate. The ketone body had little or no effect on the basal or the maximally insulin-stimulated rate of transport. However, beta-hydroxybutyrate potentiated the effect of submaximal concentrations of insulin, i.e., it resulted in a leftward shift in the dose-response curve. The half-maximally effective concentration of insulin was decreased by approximately 30% from 0.58 ng/ml to 0.40 ng/ml. beta-Hydroxybutyrate caused a slight (approximately 10%) increase in 125I-insulin binding to the cells. To determine whether this small increase in insulin binding is responsible for the increased insulin sensitivity in the presence of the ketone, two mimickers of insulin action were used: a serum containing anti-insulin receptor antibodies and hydrogen peroxide. beta-Hydroxybutyrate increased the sensitivity of glucose transport to stimulation by the anti-receptor antibody, demonstrating that insulin itself does not have to be present. beta-Hydroxybutyrate also potentiated the effect of hydrogen peroxide (which acts at a level distal to the insulin receptor) even in cells that had been depleted of insulin receptors by trypsin treatment. Therefore, beta-hydroxybutyrate acts, at least partly, at a post-insulin receptor level. Adenosine increases the insulin sensitivity of adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Nov
PMID:beta-Hydroxybutyrate increases the insulin sensitivity of adipocyte glucose transport at a postreceptor level. 638 23

Adenosine (ADO) has been implicated as a pathophysiological factor in contrast media (CM)-induced acute renal failure, which has been encountered more often in patients with diabetes and impaired renal function. Therefore, we studied the renal vascular response to exogenous and endogenous ADO in streptozotocin-induced diabetic rats. We found that exogenous ADO (0.01-100 nmol), injected into the abdominal aorta, decreased renal blood flow (RBF) in a dose-dependent manner. The dose-response curve was shifted to the left by factor 30 in diabetic, compared with nondiabetic rats rats. Renal vascular response to endogenous ADO, assessed by postocclusive reduction of RBF after a 30-s renal artery occlusion, was significantly enhanced (P < 0.001) in diabetic rats (75.6 +/- 3.9%) compared with nondiabetic rats (36.5 +/- 2%). ADO A1-receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine attenuated exogenous and endogenous ADO-induced renal vasoconstriction in both groups. We conclude that the ADO A1-receptor signal-transduction chain is altered in diabetic animals and that the enhanced vasoconstrictive action of ADO could be involved in the kidney pathophysiology of diabetes mellitus.
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PMID:Increased sensitivity of the renal vasculature to adenosine in streptozotocin-induced diabetes mellitus rats. 748 38

Adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) mediate penile erection. We have previously established that adenylate and guanylate cyclase activity is elevated in the diabetic rat penis and aorta. This study investigates the action of papaverine and vasoactive intestinal polypeptide (VIP) on these cyclases. The aortae and penes of Sprague Dawley rats (n = 7) were stimulated with VIP and papaverine. Diabetes mellitus (DM) was induced in Sprague Dawley rats (n = 7) with streptozotocin and the penile and aortic tissues were treated with VIP. The penes, aortae and carotid arteries of New Zealand White rabbits were similarly processed. cAMP and cGMP generation was measured by radioimmunoassay. In all tissues: VIP stimulated cAMP synthesis; VIP did not increase cGMP levels; papaverine was without effect on either cAMP or cGMP synthesis. VIP-stimulated cAMP was significantly enhanced in the diabetic rat penis and aorta; there was also a significant elevation in the basal levels of cGMP in these tissues. These data: (1) consolidate that cAMP is a mediator of penile erection, (2) indicate that papaverine and VIP elicit erection by different mechanisms, (3) suggest that an enhanced penile capacity to generate cAMP in DM may constitute an adaptive response to counteract the previously reported reduction in VIP content and VIP receptors, and (4) indicate that the penile and vascular tissues of the rabbit respond in a similar manner to VIP and papaverine.
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PMID:Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study. 749 46

The dose response effect of a new adenosine analogue, GR79236 (N-[1S trans-2-hydroxycyclopentyl] adenosine) upon insulin sensitivity was examined in human adipocytes. The influence of adenosine upon insulin sensitivity for suppression of lipolysis and stimulation of glucose transport was examined. Removal of adenosine by use of adenosine deaminase stimulated lipolysis to the same extent as did 10(-9) M noradrenaline. GR79236 brought about dose dependent inhibition of lipolysis with half-maximal effect at 11.3 +/- 7.8 x 10(-9) M. When lipolysis was stimulated by noradrenaline alone the subsequent inhibition of lipolysis brought about by GR79236 was significantly greater than that of insulin. To examine adenosine effects on the insulin signalling pathway separately from those on lipolysis, the insulin sensitivity of glucose transport was examined. Removal of adenosine brought about a small but significant increase in the concentration of insulin required for half-maximal stimulation of glucose transport. Adenosine agonists offer promise as new agents for the modulation of metabolism in diabetes and other states of insulin resistance.
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PMID:Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes. 762 86


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