Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TOLBUTAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1985

The effect of some benzimidazoles on the disposition of antipyrine and tolbutamide from the rat isolated perfused liver.

The anthelmintic benzimidazoles, mebendazole, albendazole and flubendazole have been screened for any propensity to alter the disposition of antipyrine and tolbutamide in the rat isolated perfused liver preparation. The benzimidazoles were added as a 2.5 mg bolus dose into the perfusate reservoir 5 min before the administration of either antipyrine or tolbutamide. Neither mebendazole or albendazole produced any significant effect on the pharmacokinetics of either of the substrate drugs. In contrast, flubendazole significantly decreased the clearance of antipyrine (by 40%) indicating inhibition of mixed function oxidase activity. However, flubendazole did not alter the disposition of tolbutamide. The results suggest that not all benzimidazoles inhibit hepatic drug metabolizing enzymes and that different forms of cytochrome P-450 are involved in the metabolism of antipyrine and tolbutamide.

Animals↗
PubMed1993

A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea.

We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p-formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg-1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3-(p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit.

Animals↗
PubMed1989

Tolbutamide reverses hypoxic pulmonary vasoconstriction in isolated rat lungs.

We have investigated the effects of tolbutamide on the hypoxic vasoconstriction of isolated, perfused rat lungs. We did this because lowered ATP may link hypoxia and constriction, and tolbutamide mimics the effects of ATP in other tissues by blocking ATP-sensitive potassium (ATP-K) channels. Pulmonary vasoconstriction, induced by lowering the oxygen of the gas ventilating the lungs from 95 to 2%, was always reduced or abolished by tolbutamide (1.7 x 10(-4)-8.5 x 10(-3) M). High concentrations (greater than or equal to 10(-3) M) of diazoxide, a drug that opens ATP-K channels, dramatically constricted the pulmonary vasculature and this effect was also reversed by tolbutamide. The opening of ATP-K channels may therefore underlie hypoxic pulmonary vasoconstriction.

Adenosine Triphosphate↗
PubMed2002

Effect of albumin and cytosol on enzyme kinetics of tolbutamide hydroxylation and on inhibition of CYP2C9 by gemfibrozil in human liver microsomes.

The effect of human serum albumin (Hsa) and human liver cytosol (Hlc) on the in vitro enzyme kinetics of the formation of hydroxytolbutamide (CYP2C9 marker reaction) and the inhibitory effect of gemfibrozil on tolbutamide hydroxylation were examined using human liver microsomes. The addition of Hsa greatly decreased the unbound concentrations of tolbutamide and gemfibrozil in the incubation medium, whereas Hlc only slightly decreased them. The unbound K(m) value for tolbutamide hydroxylation was 123 microM without Hsa and Hlc, and 73, 88, and 64 microM in the presence of Hsa (5 mg/ml), Hlc (0.5 mg/ml), and Hsa plus Hlc, respectively. The predicted in vivo hepatic clearance (CL(h)) of tolbutamide based on enzyme kinetics without Hsa and Hlc (0.06 ml/min/kg) was 40% of its in vivo clearance (0.15 ml/min/kg) based on published data. Addition of 5 mg/ml Hsa and 0.5 mg/ml Hlc to the incubation medium distinctly improved the prediction, with the coaddition of Hsa and Hlc yielding the most accurate value (0.14 ml/min/kg). The K(i) (6 microM) of gemfibrozil for CYP2C9, calculated using total drug concentrations, was increased by Hlc (8 microM), Hsa (40 microM), or both (72 microM). However, when the unbound substrate and inhibitor concentrations were considered, the K(i) (6 microM without Hsa and Hlc) was not markedly altered by Hsa (4 microM), Hlc (8 microM), or both Hsa and Hlc (9 microM). The present findings suggest that the addition of Hsa and Hlc to microsomal incubation media may yield enzyme kinetic estimates more comparable with in vivo results.

Albumins↗
PubMed1983

Effect of tolbutamide on myocardial energy metabolism.

Exposure of rat hearts perfused with 5 mM glucose and 5 mM acetate to tolbutamide led to a dramatic stimulation in glucose utilization and glycolytic flux. This effect was concentration dependent, with the largest response occurring at a tolbutamide concentration of 0.6 mM. Measurement of tissue glycogen content revealed that the higher concentrations of tolbutamide also enhanced glycogenolysis, indicating that the increase in glycolysis was caused by an increase in both glucose consumption and glycogen mobilization. On the basis of the determination of key metabolic intermediates, it was concluded that the stimulation of anaerobic metabolism was mediated by an activation of both phosphofructokinase and phosphorylase. The observed increase in glycolytic flux was associated with a rise in lactate production; however, the most pronounced effect of the drug was the stimulation of glucose oxidation. Thus the percentage of oxygen used in the oxidation of glucose was dramatically increased. Calculations also revealed that the contribution of glucose to overall ATP production rose from 8% in the absence of tolbutamide to about 30% in the presence of the sulfonylurea.

Adenine Nucleotides↗
PubMed2000

Effects of adrenaline and tolbutamide on insulin secretion in INS-1 cells under voltage control.

The aim of the present study was to investigate whether mechanisms distal to the regulation of Ca2-influx are involved in tolbutamide-induced stimulation and adrenaline- and somatostatin- induced inhibition of insulin secretion in INS-1 cells. Using the patch clamp method, the membrane voltage was either kept constant at -70 mV, or Ca2+-influx was activated by short depolarising pulses to 0 my. These pulses induced an increase in cellular capacitance (Cm) caused by fusion of secretory granules with the plasma membrane. Tolbutamide did not alter, neither Cm under voltage clamp at -70 mV nor increases of Cm due to voltage pulses. The inhibitors of secretion, adrenaline and somatostatin, counteracted the augmentation of [Ca2+]i which was induced by glucose, tolbutamide and forskolin. In the voltage clamp mode, however, where no changes of [Ca2]i. were observed, adrenaline but not somatostatin inhibited the increase of Cm caused by depolarizing voltage pulses. The adrenaline effect on Cm was dependent on the addition of GTP to the pipette solution. When GTP was replaced by GDPbetaS or GTPgammaS, the effect of adrenaline on Cm was abolished. The blockade of calcineurin, by the addition of calcineurin inhibitory peptide (CIP) to the pipette solution, did not affect the adrenaline-induced inhibition of Cm. Moreover. After incubation of the cells with deltamethrin, a calcineurin inhibitor, the stimulation of secretion was attenuated, but the adrenaline-induced inhibition was not affected. Our results suggest that adrenaline-induced inhibition of insulin secretion involves a site of action directly related to the exocytotic membrane fusion. In contrast, the stimulator tolbutamide and the inhibitor somatostatin had no direct effect on exocytosis in INS-1 cells.

Cell Line↗
PubMed1977

The effects of tolbutamide on the myocardium in experimental diabetes.

The effects of chronic tolbutamide treatment were examined in a diabetic animal model in which abnormal myocardial function and composition have previously been demonstrated. Eight diabetic dogs were given tolbutamide 250 mg/day orally and compared with seven untreated diabetics, five healthy dogs receiving tolbutamide, and eight normal controls. After one year, resting hemodynamic studies in the intact anesthetized state showed that treated diabetic dogs had a significantly higher left ventricular end-diastolic pressure of 12.1+/-1.3 mm Hg associated with normal end-diastolic volume, compared to 6.1+/-0.8 mm Hg in untreated diabetics (P less than 0.01) and 6.3+/-0.5 in normals. Stroke work and ejection fraction were similar to normals. Acute volume expansion revealed a larger rise of left ventricular end-diastolic pressure in treated and untreated diabetics than normals, without a significant stroke volume response in treated diabetics. Enhanced stiffness of myocardium appeared to be related to interstitial accumulation of periodic acid-Schiff staining material, further intensified in treated diabetics by triglyceride accumulation observed on electron microscopy and by chemical analysis. Thus treatment of diabetes with tolbutamide, despite improved glucose tolerance, effected further reduction of left ventricular function and altered morphology of myocardium.

Animals↗
PubMed1983

Tolbutamide perifusion of rat islets. Sequential changes in calcium, phosphorus, sodium, potassium, and chlorine in single beta cells.

Fluctuations of calcium, phosphorus, sodium, potassium, and chlorine in beta cells were followed during rat islet perifusion with tolbutamide and related to insulin secretion. In 24 paired experiments two chambers containing 100 islets were perifused with buffered medium containing 4.2 mM glucose alone or with added tolbutamide (200 micrograms/ml). Effluent was collected frequently for insulin determinations. At eight different time intervals from 0 to 20 min islets were acutely fixed, prepared for scanning electron microscopy and beta cells in islet tissue were identified. Element content in 480 single cells was measured by energy dispersive x-ray analysis. Tolbutamide elicited typical monophasic insulin release that exceeded control islet secretory rates from 2 to 6 min with a peak value at 3 min. This pattern was preceded by monophasic calcium accumulation in beta cells that abruptly rose 150% above control cells at 1 min and declined to base line by 4 min. The rapid ascent of calcium was associated with significant depressions of sodium and potassium content without alterations of cell phosphorus. Chlorine fell at 2 min and then rose greater than 50% above control cells at 4 min. After 6 min insulin secretion and element content remained near control levels. We conclude that monophasic calcium accumulation in beta cells is the earliest, most predictive event of islet insulin secretion after a tolbutamide stimulus. Oscillations of beta cell sodium and potassium reciprocally relate to calcium, and an elevation of chlorine content is a relatively late phenomenon in the stimulus-secretion coupling process.

Animals↗
PubMed2006

Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers.

This study was undertaken to clarify the influence of repeated oral administration of Ginkgo biloba extract (GBE) on CYP2C9 and CYP3A4. CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide. Plasma drug concentrations and blood glucose levels were measured. The area under concentration versus time curve (AUC0-infinity) for tolbutamide after GBE intake was slightly but significantly (16%) lower than that before GBE intake. Concomitantly, GBE tended to attenuate AUC0-2 of blood glucose-lowering effect of tolbutamide. AUC0-infinity for midazolam was significantly (25%) increased by GBE intake and oral clearance was significantly (26%) decreased. Thus, it is suggested that the combination of GBE and drugs should be cautious in terms of the potential interactions, especially in elderly patients or patients treated with drugs exerting relatively narrow therapeutic windows.

Adult↗
PubMed1983

Suppression of glucagon secretion during a tolbutamide infusion in normal and noninsulin-dependent diabetic subjects.

To determine the effect of tolbutamide on glucagon release in noninsulin-dependent diabetic and normal subjects and how plasma glucose levels may modulate this effect, the acute glucagon response (AGR) to a 5-g iv arginine pulse was determined before and during a tolbutamide infusion. There was a decrease in plasma glucose concentration in both normal and diabetic subjects (both P less than 0.001); there tended to be a suppression of the AGR (4 of 6 normals and 8 of 11 diabetics), but this suppression was not statistically significant. In separate studies, when the plasma glucose level was clamped at baseline values by a variable rate of glucose infusion, the AGR was suppressed during the tolbutamide infusion in all 7 normal [change in AGR (delta AGR) = -35 +/- 12 pg/ml; P less than 0.05] and all 6 noninsulin-dependent diabetic subjects (delta AGR = -14 +/- 5 pg/ml, p less than .05). In 6 insulin-dependent diabetic subjects, there was no evidence of glucagon suppression by tolbutamide (delta AGR = +2 +/- 2 pg/ml). These results are consistent with the hypothesis that sulfonylureas suppress glucagon secretion by augmenting insulin secretion, an effect that falling glucose levels can mask. Consideration of this observation is necessary when interpreting the effects of a sulfonylurea on islet cell responses.

Adult↗
PubMed2001

Application of the PKCYP-test to predict the amount of in vivo CYP2C11 using tolbutamide as a probe.

Previous reports have shown that the determination of drug metabolism capacity can be made by the pharmacokinetic estimation of the quantity of cytochrome P450 (CYP) in vivo (PKCYP-test), in which an apparent liver-to-blood free concentration gradient in vivo (qg) is introduced, which is useful for evaluating fluctuations of CYPIA2 in rats. The aim of the present study was to examine the application of the PKCYP-test to evaluate the quantity of in vivo CYP2C11 by using tolbutamide as a probe, to confirm its validity using a physiologically-based pharmacokinetic rat model. Rats treated with carbon tetrachloride (CCl4-treated rats) were used as a model for low levels of CYP2C11 in the liver. In CCl4-treated rats, the total body clearance (CLtot) of tolbutamide and the amount of CYP2C11 fell to about a quarter and a third of that in control rats, respectively. The time-course of tolbutamide concentrations in serum in control rats could be simulated by a physiologically-based pharmacokinetic model. In CCl4-treated rats, take into consideration the qg value of control rats, the level of CYP2C11 was accurately predicted by the PKCYP-test, and the time-course of tolbutamide concentrations in serum could be predicted by the same physiologically-based pharmacokinetic model. In conclusion, we have shown that the PKCYP-test can be used to predict levels of CYP2C11. It was also demonstrated that the qg and amount of CYP are useful parameters in the PKCYP-test by constructing a physiologically-based pharmacokinetic model which was applied to the PKCYP-test.

Animals↗
PubMed1982

Amylase release from parotid glands of hypothyroid rats. II. Phosphorylation of microsomal proteins and effects of adenosine 3',5'-monophosphate and tolbutamide.

The present study was undertaken to examine the phosphorylation of the parotid microsomal fraction from normal and hypothyroid rats and also to compare the effects of cyclic AMP and tolbutamide on the protein phosphorylation in the two groups. After incubation in the presence of cyclic AMP, an increased rate of phosphorylation of three protein bands was revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. The apparent molecular weights of these proteins were 33,500, 26,000 and 19,000. The small protein band of 17,000 daltons decreased in 32P incorporation in the presence of cyclic AMP. Tolbutamide specifically inhibited 32P incorporation into the three proteins from normal rats, whereas the rate of phosphorylation of these proteins from hypothyroid rats remained essentially the same as that of the control, even in the presence of tolbutamide. These findings strongly suggest the possibility that stimulation of amylase release by the beta-adrenergic agonist or cyclic AMP was associated with phosphorylation of the three parotid microsomal proteins and that cyclic AMP-dependent, tolbutamide-resistant phosphorylation of these proteins from hypothyroid rats plays an important role in the increased responsiveness to beta-adrenergic stimulation.

Adenosine Triphosphate↗
PubMed1977

Studies on diabetic syndrome and influences of long-term tolbutamide administration in Mongolian gerbils (Meriones unguiculatus).

Sixty-seven mongolian gerbils (Meriones unguiculatus), which seem to resemble the sand rats in the manifestation of diabetic syndrome, were used for observations on the development of diabetic process and on the effect of the long term administration of tolbutamide on it. The mean blood glucose (158.2 +/- 14.7 mg/100 ml), mean serum NEFA (0.70 +/- 0.34 mEq/l) and mean serum IRI (68.9 +/- 10.2 muU/ml) in mongolian gerbils were relatively higher than those in rats. Diabetes-like processes found in the pancreas of mongolian gerbils were roughly grouped into two main types: (1) the histopathological process in which the fibrosis, initially prominent at perivascular space, spread to the islets, finally producing the islet's cell degeneration, and (2) the process of diffuse islet's hyperplasia. These two processes were considered to differ from each other, the former being affected by tolbutamide and the latter remaining unaffected. After breeding on the diet containing 0.1 -0.2% tolbutamide for 6 months, there was a general inclination of an increase of cases of severe pathological findings, and the distribution probabilities of the cases carrying the severe fibrotic process in heart, that is, the process from endothelial cell swelling, medial fibrosis and obliterative changes in cardiac arteries which was resulting in the focal degeneration of cardiac muscle, was significantly higher than in the non-treated group. It was concluded that mongolian gerbil might be recommended as a model of experimental diabetes and that tolbutamide seemed to have some harmful effects on the diabetes-like process in mongolian gerbils.

Animals↗
PubMed1991

Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats.

The chronic effects of tolbutamide on myocardial contractility of the diabetic heart during ischemia and reperfusion were evaluated in perfused, isolated rat hearts. Five experimental groups were used: (1) control rats (C), (2) insulin dependent diabetic rats (IDDM, single intravenous injection of 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley rats), (3) non insulin dependent diabetic rats (NIDDM; single subcutaneous injection of 90 mg/kg STZ in 5 day neonates), (4) tolbutamide-treated IDDM and (5) NIDDM (T-IDDM, T-NIDDM; giving tolbutamide 100 mg/kg/day for 6 weeks via an orogastric tube every day, respectively). At 14 weeks of age, experiments were performed using a Langendorff perfused heart preparation. After equilibration, T (myocardial developed tension), +dT/dt (contraction velocity), -dT/dt (relaxation velocity) and RT (resting tension) were measured during a 15 min period of global ischemia, followed by reperfusion for 20 min. Basal values of T increased in both T-IDDM and T-NIDDM, compared to IDDM and NIDDM, respectively. The percent recovery rate of +dT/dt in T-IDDM increased significantly during both ischemia and reperfusion, but the change in T-NIDDM was not significant. The recovery rates of -dT/dt in T-IDDM and T-NIDDM were significantly higher throughout reperfusion than in IDDM and NIDDM, respectively. On the other hand, that of T in T-IDDM and T-NIDDM were significantly higher than IDDM and NIDDM throughout ischemia and reperfusion, respectively. The RT was significantly higher in IDDM than in C and NIDDM throughout ischemia and reperfusion. The RT was significantly lower during ischemia in IDDM, but it did not differ significantly from IDDM during reperfusion. These results indicate that chronic oral administration of tolbutamide directly improved myocardial contractility throughout ischemia and reperfusion regardless of the improvement of glycemia. The improvement was also greater in IDDM than in NIDDM.

Animals↗
PubMed1977

Insulin response to glucose or glucagon in subclinical diabetes previously injected with tolbutamide.

Thirty-one patients with subclinical diabetes, who showed diabetic or impaired glucose tolerance after treatment for diabetes, were investigated in order to clarify the abnormalities of insulin response in diabetes mellitus. These patients showed a delayed response of plasma insulin during oral glucose loading. In the tolbutamide-glucose test, in which glucose loading followed the intravenous tolbutamide injection at a 60-min interval, the insulin level at 90 min was significantly lowered in a group of 20 patients with subclinical diabetes. In the tolbutamide-glucagon test, in which 1 mg of glucagon was injected 60 min after tolbutamide injection, the maximal level of plasma insulin was significantly decreased in a group of 10 subclinical diabetes except for one patient. These results indicate that insulinogenesis and/or release of insulin were decreased even in subclinical diabetes, suggesting that such a defect in islet function might be one of the abnormalities in primary diabetes.

Blood Glucose↗
PubMed1982

Insulin response to glucagon with or without tolbutamide in normal and diabetic subjects.

In order to investigate insulin response to glucagon, eight normal subjects and thirty diabetic patients were studied. According to fasting blood glucose, diabetic patients were classified into three groups; mild, moderate and severe. An oral glucose tolerance test, a glucagon test and a tolbutamide-glucagon test were performed at intervals of several days. In the glucose tolerance test, insulin response was reduced in the patients with moderate or severe diabetes. Plasma insulin increased and reached a peak 3 min after glucagon injection (glucagon 1) in the normal controls (66.1 +/- 9.9 microunits/ml), while plasma insulin response to glucagon 1 was reduced in the three diabetic groups (35.8 +/- 7.3, 33.2 +/- 9.7 and 22.9 +/- 5.0 microunits/ml, respectively). In the normal subjects glucagon injected 60 min after tolbutamide (glucagon 2) caused a rise in insulin (72.0 +/- 4.9 microunits/ml). In the diabetic groups, glucagon 2 caused a reduced response of plasma insulin (38.6 +/- 8.9, 49.5 +/- 17.4 and 34.8 +/- 11.3 microunits/ml, respectively). Glucagon with or without tolbutamide produced a far greater maximal response of plasma insulin in all the diabetic groups than in the normal subjects, while glucose produced a not significantly different increment of plasma insulin between the normal subjects and the mild diabetics. The present study demonstrates the glucagon injection with or without tolbutamide could clearly discriminate the insulin response in diabetics from that in normal subjects.

Adult↗
PubMed1980

Ten-year follow-up of subjects with impaired glucose tolerance: prevention of diabetes by tolbutamide and diet regulation.

In a diabetes detection survey carried out between 1962 and 1965, 2477 (1.1%) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal. Of these 2477, 578 displayed impaired tolerance to oral glucose without having manifest diabetes. From this group, 267 men were divided into five groups and subjected to the following treatments and controls: (a) diet regulation and 0.5 g tolbutamide t.i.d. (N = 49), annual oral glucose tolerance test (OGTT); (b) diet regulation and one placebo tablet t.i.d. (N = 48), annual OGTT; (c) diet regulation only (N = 50), annual OGTT; (d) no treatment (N = 61), annual OGTT; and (e) no treatment, OGTT at follow-up (N = 59 at follow-up). In addition, a control group was included comprised of men with normal OGTT (N = 52). At follow-up, 29% of those without diet regulation and medication (group e: N = 59) had developed diabetes. Of those on diet regulation, but without active medication (group b plus group c, N = 98), 13% had diabetes. No individual maintaining tolbutamide and diet regulation (N = 23) had progressed to diabetes. In this group, 80% of those later examined (N = 11) had serum tolbutamide concentrations in the therapeutic range. No individual with initially normal OGTT developed diabetes or impaired OGTT. The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes, whereas impaired glucose tolerance is associated with a high risk of progression to diabetes. In addition, it seems possible that treatment with diet regulation, in combination with tolbutamide, may prevent or postpone progression from impaired glucose tolerance to manifest diabetes.

Diabetes Mellitus↗
PubMed1983

Impact of insulin or tolbutamide treatment on 14C-arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats.

Diabetes is associated with a dramatic increase in the risk of thrombotic and atherosclerotic disease. The underlying factors responsible for this predisposition as well as the mechanisms involved have yet to be elucidated. Two endogenous substances, prostacyclin (PGI2) and thromboxane (TXA2), have recently been shown to possess significant vascular and thrombotic activity and are known to be altered in atherosclerosis, thrombotic conditions, and diabetes. We determined the conversion of 14C-arachidonic acid (AA) to PGI2 and TXA2 by lungs, aortas, and platelets obtained from chemically induced diabetic rats. In addition, we investigated the ability of insulin or tolbutamide to reverse these changes. Streptozotocin (STZ)-injected rats developed blood glucose levels 2-4 times that seen in normoglycemic controls. Intact perfused lungs isolated from rats beginning 7 days after STZ treatment synthesized 22-30% less PGI2 from 14C-AA. The ratio of PGI2/TXA2 was decreased in the diabetic rat lungs and was inversely proportional to plasma glucose levels at the time of death. Platelet TXA2 generation was increased 67% above control in diabetic rats while aortic PGI2 generation was decreased 28% below normoglycemic controls. Ten-day treatment with NPH insulin 20 U/kg s.c. in STZ-pretreated rats lowered plasma glucose toward normoglycemia more effectively than tolbutamide 200 mg/kg orally. Partial correction of the decreased pulmonary PGI2/TXA2 ratio seen in diabetic rats was produced by insulin and tolbutamide in proportion to their ability to lower blood glucose. At the doses employed, insulin caused aortic PI2 and platelet TXA2 generation from 14C-AA to approach that seen in mormoglycemic controls more effectively than tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗