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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In diabetic rats glomerular morphologic damage is exacerbated by feeding a protein-rich diet. Protein feeding alters arachidonic acid metabolism in other models of renal disease, and there is evidence that the arachidonic acid metabolite thromboxane plays a pathophysiologic role in protein-induced renal injury. In this study we evaluated the effect of high-protein feeding on renal thromboxane production, renal hemodynamics, and renal morphologic condition in rats with experimentally induced diabetes. We induced diabetes in male Sprague-Dawley rats by streptozocin administration. Rats then received high (60% casein)- or low (8% casein)-protein diets. Eight to 11 weeks later, clearance of inulin and PAH and renal blood flow were measured. Rats fed 60% casein had higher glomerular filtration rate and renal blood flow than rats fed low-protein diets. Rats fed high-protein diets had more glomerular hypercellularity, tubular hypertrophy, and arteriolar thickening than their protein-restricted counterparts. Renal production of 6-keto-PGF1a and PGE2 was not different between dietary groups. Renal thromboxane production, however, was greater in rats fed 60% protein than in rats fed 8% protein. We conclude that protein feeding stimulates renal thromboxane production and exacerbates morphologic injury in the diabetic rat. Short-term administration of the thromboxane synthetase-inhibitor UK 38,485 did not further increase glomerular filtration rate or renal blood flow in animals fed high protein. Thus thromboxane did not appear to play a role in protein-induced injury in this model by a vasoconstrictive mechanism. Other possible mechanisms by which thromboxane may contribute to the renal damage observed are discussed.
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PMID:High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes. 280 97

Prostaglandin E2 (PGE2) inhibits glucose-induced insulin secretion, and inhibitors of PGE2 synthesis augment this event. However, there has been confusion regarding prostaglandin regulation of insulin secretion, partly because no mechanism has been demonstrated for the inhibitory action of PGE2 on beta-cell function. These studies were performed with a clonal cell line of glucose-responsive beta-cells (HIT cells) to determine whether PGE2 effects on insulin secretion are receptor mediated and, if so, whether the postreceptor effects are mediated by inhibitory regulatory components (Ni) of adenylate cyclase. Saturable [3H]PGE2 binding to HIT cells was demonstrated. This binding was dissociable and specific for prostaglandins of the E series. Scatchard analyses of binding data indicated a single class of sites with a Kd of approximately 1 X 10(-9) M. Guinea pig islets were also demonstrated to have a single class of binding sites with a similar Kd but only 22% as many binding sites (0.060 vs. 0.013 pmol/mg protein, HIT cells vs. guinea pig islet). HIT cells were demonstrated to synthesize PGE2, and this synthesis was inhibitable by acetylsalicylic acid. Accumulation of cAMP by HIT cells was inhibited in a concentration-dependent manner by PGE2 with an IC50 of approximately 1 X 10(-9) M. Insulin secretion by HIT cells during static incubations with 11.1 mM glucose was also inhibited by PGE2 in a concentration-dependent manner with an IC50 of 1 X 10(-9) M. PGE2 was more potent than epinephrine but less potent than somatostatin in this regard. Maximum inhibition of glucose-induced insulin secretion was 26, 37, and 29% of control values for somatostatin, PGE2, and epinephrine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Sep
PMID:Receptor-mediated adenylate cyclase-coupled mechanism for PGE2 inhibition of insulin secretion in HIT cells. 288 85

The effect of dihomogammalinolenic acid (DHLA) administration on platelet aggregation and prostaglandin production, erythrocyte fatty acid composition and serum lipids was compared in healthy subjects and insulin-dependent diabetics (IDDs). In healthy subjects, DHLA caused a significant inhibition of ADP-induced platelet aggregation and an increase in platelet PGE1 release; IDDs did not show these changes. There were no differences, however, in platelet thromboxane A2 (TXA2) or PGE2 release between healthy subjects and IDDs before and after DHLA. Following DHLA, the arachidonic acid content of erythrocytes increased in healthy subjects; this increase was not observed in IDDs. DHLA induced a significant fall in serum non-esterified fatty acid concentrations in both groups without altering either cholesterol or triglyceride concentrations. These data show for the first time that IDD platelets may have a specific defect of PGE1 synthesis quite distinct from the delta 5- and delta 6-desaturase defects known to be associated with experimental diabetes; this defect may contribute to platelet hyper-aggregability in diabetes; and DHLA has a potent antilipolytic effect in vivo; and erythrocytes from IDDs may have a delta 6-desaturase defect.
Diabetes Res 1986 Jan
PMID:The effect of dihomogammalinolenic acid on platelet aggregation and prostaglandin release, erythrocyte membrane fatty acids and serum lipids: evidence for defects in PGE1 synthesis and delta 5-desaturase activity in insulin-dependent diabetics. 293 1

Diabetes has been shown to result in reduced prostacyclin synthesis by macrovascular tissue in rats and humans. Other studies have shown that plasma levels of 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) and synthesis of 6-keto-PGF1 alpha by isolated glomeruli are either unchanged or increased in diabetes. Thus, microvascular tissue may respond differently to diabetes than macrovascular tissue. Accordingly, we have studied the effects of streptozotocin-induced diabetes mellitus on prostaglandin synthesis by rat cerebral microvessel (RCMV). Prostaglandin synthesis from both endogenous and exogenous arachidonic acid was determined. The yield of RCMV from diabetic and control animals was similar. Under basal conditions and following stimulation of prostaglandin synthesis by melittin (5 micrograms/ml), RCMV production of prostacyclin (measured as immunoreactive 6-keto-PGF1 alpha) was greater than production of PGE2. Both 6-keto-PGF1 alpha and PGE2 production under basal and stimulated conditions were found to be similar for control and diabetic RCMV. The RCMV converted exogenous [3H]arachidonic acid predominately to PGD2 and to a lesser extent to 6-keto-PGF1 alpha. No significant differences in the conversion of exogenous [3H]arachidonic acid to PGD2 and 6-keto-PGF1 alpha was observed between control and diabetic RCMV. This study suggests that the effect of streptozotocin-induced diabetes mellitus on prostaglandin formation by microvascular endothelium is different from its effect on macrovascular tissue.
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PMID:Effect of streptozotocin-induced diabetes on prostaglandin production by rat cerebral microvessels. 294 Jul 27

The effect of streptozotocin-induced diabetes mellitus (DM) on rat brain prostanoid synthesis was assessed. Prostacyclin (PGI2) synthesis was significantly reduced in the DM animals in all 3 brain regions studied (cerebrum; cerebellum; brain stem). In contrast, the synthesis of the other 3 prostanoids assessed (PGF2 alpha; PGE2; TXA2) was not significantly altered in the DM animals. Insulin treatment reverted PGI2 synthesis towards the normal pattern. Since PGI2 is a vasodilator and the other 3 prostanoids (PGF2 alpha; PGE2; TXA2) are cerebral vasoconstrictors, these changes may be relevant to the pathogenesis of the previously reported abnormalities of cerebral blood flow and the increased incidence of cerebrovascular disease in DM.
Diabetes Res 1987 Oct
PMID:Changes in eicosanoid synthesis in the cerebrum, cerebellum and brain stem of the diabetic rat. 296 1

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3',5'-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2. Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Mar
PMID:Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes. 298 82

The islets of Langerhans have the enzymatic equipment permitting the synthesis of the metabolites of arachidonic acid: cyclo-oxygenase and lipo-oxygenase. Numerous studies have shown that cyclo-oxygenase derivatives, mainly PGE2, reduce the insulin response to glucose whereas lipo-oxygenase derivatives, mainly 15-HPETE, stimulate insulin secretion. So, for instance, drugs that increase prostaglandins synthesis as colchicine or furosemide inhibit insulin secretion while non steroid anti-inflammator drugs, mainly salicylates, which inhibit cyclo-oxygenase, enhance the insulin response to various stimuli. In type-2 (non insulin-dependent) diabetes, an increased sensitivity to endogenous prostaglandins has been proposed as a possible cause for the insulin secretion defect which characterizes this disease. Play in favor of this hypothesis the fact that the administration of PGE inhibits the insulin response to arginine in type-2 diabetics but not in normal subject and the fact that the administration of salicylates could improve the insulin response to glucose in some of these patients.
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PMID:[Prostaglandins, insulin secretion and diabetes mellitus]. 307 92

Nonketotic diabetes mellitus (DM) is associated with increased platelet production of thromboxane (TX) A2 and decreased endothelial production of prostacyclin (prostaglandin [PG]I2), but measurements of stable derivatives of these substances in the circulation have yielded discordant results. We studied the relationship between the severity of nonketotic DM and the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha, and TXB2 (stable derivatives of PGE2, PGI2, and TXA2, respectively) in rats, using three commonly employed doses of streptozotocin (40, 50, and 60 mg/kg body weight) to induce nonketotic DM of varying severity. Small differences in the severity of DM were associated with considerable differences in the plasma levels of 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1 alpha but not TXB2. Each eicosanoid responded differently to variations in the severity of DM. The plasma 13,14-dihydro-15-keto-PGE2 level was significantly lower than normal in the rats given 40 mg/kg streptozotocin, was unchanged from normal in the rats given 50 mg/kg and was significantly higher than normal in the rats given 60 mg/kg. The plasma 6-keto-PGF1 alpha level was significantly increased in rats given 40 mg/kg and 60 mg/kg, but was unchanged in those given 50 mg/kg. The plasma TXB2 level was not significantly different from normal in any one of the three groups of rats with nonketotic DM. The effect of severity on the plasma levels of the PGE2 and PGI2 derivatives is unexplained, but may reflect the origin of these derivatives from diverse organs and tissues, and the differing effects of abnormal metabolic factors (eg, fatty acids, glucose, insulin, pH) on the synthesis of these derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma eicosanoid levels in rats with nonketotic diabetes mellitus: effect of severity. 308 95

Plasma levels of 13,14-dihydro-15-keto-PGE2, a stable derivative of PGE2, are elevated in rats with diabetic ketoacidosis (DKA) and decrease in response to insulin therapy. In patients with insulin-dependent diabetes mellitus type I (IDDM) the plasma levels of this derivative also rise in response to insulin withdrawal and then fall in response to insulin replacement. We wished to determine whether the level of this substance is elevated acutely when patients present with DKA and to determine whether the levels fall during treatment. We also wished to identify the origin of the circulating 13,14-dihydro-15-keto-PGE2 in patients with DKA and in normal fasting subjects. We measured the plasma level of 13,14-dihydro-15-keto-PGE2 in five patients with DKA and in six normal subjects during a 24-h fast. In the patients with DKA before treatment, the plasma 13,14-dihydro-15-keto-PGE2 level was threefold above normal. During therapy, the 13,14-dihydro-15-keto-PGE2 level fell toward normal. There was a significant direct correlation between the plasma free fatty acid (FFA) level and the plasma 13,14-dihydro-15-keto-PGE2 level before and during treatment. In addition, the inverse correlation between the plasma free-insulin level and the plasma 13,14-dihydro-15-keto-PGE2 level approached significance (P = .06). In contrast, in the normal fasting subjects the plasma FFA level rose to values comparable to those observed in the patients with DKA, but there was no significant increase in the plasma 13,14-dihydro-15-keto-PGE2 level.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Sep
PMID:Plasma level of 13,14-dihydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjects. 309 34

1. Previous studies have demonstrated that the administration of prostaglandins (PGs) inhibits insulin secretion in vivo and have suggested that these compounds may be involved in the pathogenesis of diabetes mellitus. The present study was carried out in order to explore the effect of PGE2 on sulfonylurea-induced insulin release. 2. We determined glycemia and insulinemia in rat blood samples, at different times before and after the intraarterial administration of: (a) glibenclamide, (b) tolbutamide, (c) PGE2, (d) glibenclamide and PGE2, (e) tolbutamide and PGE2; in all cases with and without a glucose pulse. (Glibenclamide 0.5 mg/kg, tolbutamide 50 mg/kg, PGE2 100 micrograms/kg and glucose 500 mg/kg). 3. The results of these experiments demonstrate that PGE2 partially inhibits sulfonylurea-induced insulin release. The plasma insulin and glucose levels remain within the range of intermediate values as compared to the control groups (sulfonylurea or PGE2-treated rats) both in presence and absence of glucose.
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PMID:Effect of PGE2 on sulfonylurea induced insulin release. 312 43


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