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

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment. 205

An enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against surface components of rat islet and spleen lymphocytes. Live islet tumor RIN5 AH cells expressing characteristic ganglioside target antigens or rat spleen cells were immobilized onto wells of microtiter polystyrene plates precoated with poly-l-lysine and then incubated with test or normal rat sera. Cell surface-bound antibodies were quantitated after reaction with horseradish peroxidase-conjugated rabbit anti-rat Ig. With this assay, 46% (6/13) of sera from diabetes-prone BB rats and 100% (8/8) of sera from rats treated with complete Freund's adjuvant/streptozotocin (CFA/STZ) prior to immunization with RIN cells had islet cell surface antibodies: 54% (7/13) and 75% (6/8), respectively, were positive for lymphocyte antibodies (defined as the HRP anti-rat Ig binding exceeding the mean + 2SD of control group values). SDS polyacrylamide gel electrophoresis followed by immunoblotting analysis suggested that the islet cell antibodies in sera from the BB and CFA/STZ rats recognized RIN-cell components that were different in their molecular weights. These antigens were not detectable on spleen cells indicating that the ELISA described can be used to quantitate levels of islet cell specific antibodies which possibly reflect beta cell damage with progression to islet degeneration in the rat.
 ...
PMID:Detection of antibodies to islet cell and splenic lymphocytes in diabetes-prone BB and adjuvant-streptozotocin treated Lewis rats by ELISA and immunoblot analysis. 209

The following studies examined the impact of the diabetic state on cisplatin nephrotoxicity. This study also investigated the potential mechanisms for diabetes mediated reduction of cisplatin toxicity. A diabetic state was induced in male Fischer 344 (F344) rats after intraperitoneal (i.p.) injection of 27-35 mg/kg STZ. Cisplatin (5 mg/kg, i.p.) nephrotoxicity was examined in normoglycemic and diabetic rats after 48 and 96 h. Cisplatin was nephrotoxic within 96 h to normoglycemic animals as indicated by an increased kidney weight, marked elevations in serum BUN levels as well as significant P less than 0.05) decreases in renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA). Cisplatin failed to depress renal cortical slice accumulation of PAH and TEA in the diabetic rats. Cisplatin was also less effective in increasing BUN levels or kidney weight in diabetic rats. Further studies investigated the impact of glycosuric diuresis and ketone bodies on cisplatin nephrotoxicity. Dextrose diuresis of normoglycemic rats failed to reduce the effect of cisplatin on BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA. Acetone pretreatment of normoglycemic rats also did not reduce cisplatin nephrotoxicity. These results indicate: (1) cisplatin nephrotoxicity is attenuated in the experimental diabetic state, (2) diabetes does not reduce cisplatin nephrotoxicity through glycosuric diuresis and (3) ketone body accumulation does not modulate cisplatin nephrotoxicity.
 ...
PMID:Influence of streptozotocin (STZ)-induced diabetes, dextrose diuresis and acetone on cisplatin nephrotoxicity in Fischer 344 (F344) rats. 210 3

Experimental diabetes adversely affects hypothalamic control of gonadotropin secretion and sex behavior and induces hyperphagia accompanied by severe body weight loss. Neuropeptide-Y (NPY) stimulates pituitary gonadotropin release, inhibits sexual behavior, and stimulates robust feeding in rats by acting at different sites in the hypothalamus. Therefore, we tested the hypothesis that altered hypothalamic NPY neurosecretion may mediate the constellation of effects observed in streptozotocin-induced diabetic (STZ-D) rats. Adult male rats were made diabetic by a single injection of STZ (50 mg/kg). Five months later, in vitro NPY release from the hypothalamic fragment encompassing the medial basal hypothalamus and preoptic area and NPY concentrations in seven hypothalamic sites were assessed. Basal NPY release was not significantly changed after STZ treatment. However, in response to a 30-min pulse of KCl (45 mM), NPY release from the medial basal hypothalamus-preoptic area of STZ-D rats was significantly increased compared to that in age-matched controls. In the STZ-D rats, NPY concentrations in six of the seven microdissected nuclei, including those mediating control of pituitary gonadotropin, sexual, and feeding behaviors, were increased compared to control values. In an additional study similar increments in NPY concentrations in the hypothalamic sites were observed 6 months after STZ treatment. The effects of insulin on NPY levels in microdissected hypothalamic sites in STZ-treated and BB diabetic rats was next assessed. One group of rats was treated with STZ, and the other group of rats was additionally treated with insulin (6 U/kg.day) for 3 months after development of diabetes with STZ. Again, STZ treatment alone, even for 3 months, increased NPY levels in all seven nuclei, including the suprachiasmatic nuclei. Insulin therapy completely prevented the STZ-induced increments in NPY levels in all hypothalamic sites, and the blood glucose level was 233 +/- 22 mg/dl in insulin-treated STZ-D rats and 496 +/- 6 mg/dl in untreated STZ-D rats. Similarly, NPY concentrations in five of the seven nuclei were unchanged in spontaneously diabetic BB rats (blood glucose, 435 +/- 67 mg/dl) maintained on insulin (5-8 U/kg.day). These results demonstrate that STZ-D rats have a widespread increase in NPY levels in hypothalamic sites, and there is an increase in the evoked release of NPY from the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neuropeptide-Y concentration in microdissected hypothalamic regions and in vitro release from the medial basal hypothalamus-preoptic area of streptozotocin-diabetic rats with and without insulin substitution therapy. 213 23

Microvascular disease is a hallmark of diabetes. Although the etiology of diabetic microangiopathy remains to be elucidated, numerous studies in experimental animals and human diabetic patients have suggested that a change in vascular reactivity to vasoactive agents is a component of the pathophysiology. Most previous studies have utilized indirect methods to study the microcirculation or have conducted studies of responses in large vessels. This study was designed to directly study in an intact microvascular preparation the effects of streptozocin-induced diabetes (STZ-D) on microvascular reactivity. The responses of arterioles in the cremaster muscle of pentobarbital sodium-anesthetized rats to topically applied norepinephrine were measured in STZ-D rats of 2, 4, 8, 16, and 32 wk duration and in age-matched nondiabetic rats. Resting arteriolar diameters and mean arterial pressure were not affected by diabetes. In the STZ-D rats, larger (1A) arterioles were normally responsive after 2, 4, 8, and 16 wk of diabetes compared with nondiabetic rats. In contrast, the smaller 2A and 3A arterioles exhibited hypersensitivity to norepinephrine initially, but responses returned to normal sensitivity as the duration of diabetes progressed to the chronic stage. These results suggest that there are important functional changes in the responses of the microcirculation to norepinephrine that are associated with the development of diabetes and that these changes are anatomically specific and temporally dependent.
Diabetes 1990 Mar
PMID:Microvascular reactivity to norepinephrine at different arteriolar levels and durations of streptozocin-induced diabetes. 213 2

The effect of streptozocin-induced diabetes (STZ-D) on right atrial structure was investigated in male Wistar rats. STZ (55 mg/kg) or saline (1 ml/kg) was administered by intravenous injection 12 wk before the experimental studies. Tissue was sampled from four regions of the atrium, processed, and embedded in plastic. Quantitative stereological analysis indicated that in STZ-D rats, there was a significant diminution in size of the musculi pectinati (muscular ridges), which form a network making up the wall of the atrium. In addition, within the muscular ridges, there was a significant reduction in the relative proportion of cardiocytes within the cardiac tissue. The rest of the cardiac tissue consisted of interstitial regions, connective tissue, and blood vessels, which correspondingly increased. This suggests there was some form of cardiomyopathy. When atrial granularity was determined relative to cardiocyte volume density, a significant decrease (54%) was found in tissue from STZ-D rats. The blood pressure of conscious STZ-D rats was significantly lower than control rats, whereas right atrial pressure was not different. The level of resting plasma immunoreactive atrial natriuretic factor (ANF) in conscious STZ-D rats (98 +/- 5 pg/ml) was significantly higher than in control rats (52 +/- 7 pg/ml). The decreased atrial granularity could be related to the higher resting plasma ANF levels, suggesting a more rapid turnover or increased synthesis bypassing storage in the granular form.
Diabetes 1990 Apr
PMID:Atrial structure and plasma ANF levels in rats with chronic diabetes mellitus. 213 78

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.
 ...
PMID:Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats. 213 54

Recent evidence indicates that activated T cells and macrophages play an important role in the induction of insulitis and diabetes in certain strains of mice treated with multiple subdiabetogenic doses of streptozotocin. In the present study, we treated C57BL/6J mice with five daily doses of 40 mg/ml streptozotocin and examined the prophylactic effect of an anti-interleukin 2 receptor monoclonal antibody (PC61). In mice treated with streptozotocin, interleukin 2 receptor-positive mononuclear cells were shown to infiltrate into the islets and soluble interleukin 2 receptors in the sera were significantly increased compared with control mice. The administration of PC61 to the mice attenuated the insulitis, and diminished interleukin 2 receptor-positive cells from islets and soluble interleukin 2 receptors in the sera. Moreover, the administration of PC61 significantly reduced the development of hyperglycaemia shown in these mice (12.8 +/- 1.1 mmol/l vs 18.5 +/- 0.7 mmol/l, p less than 0.005). As judged by flow cytometric analysis, this antibody did not cause any changes in either spleen cell counts or T cell subsets. Interleukin 2 receptors were expressed on a minor population of spleen cells regardless of treatment with PC61 (STZ + normal rat IgG: 2.1 +/- 0.3%, STZ + PC61: 2.4 +/- 0.3%). Even after stimulation of spleen cells with concanavalin A or alloantigen, interleukin 2 receptor expression was not significantly different between the two groups. Our studies suggest that interleukin 2 receptor-positive activated T cells or macrophages are important in the development of multi-low-dose streptozotocin diabetes and that an anti-interleukin 2 receptor antibody can attenuate this process.
 ...
PMID:Anti-interleukin 2 receptor antibody attenuates low-dose streptozotocin-induced diabetes in mice. 214 23

Voltage-sensitive Ca2+ channels in cardiac left ventricular muscle membranes isolated from nondiabetic control and diabetic rats were measured with [3H]PN 200-110, a dihydropyridine derivative, as a ligand. The binding site (Bmax) of [3H]PN 200-110 in cardiac membranes isolated from streptozocin-induced diabetic (STZ-D) rats (128 +/- 10 fmol/mg protein) significantly (P less than 0.01) increased by 64% compared with that of control rats (78 +/- 4 fmol/mg protein) 10 wk after STZ administration without a significant change in Kd. However, the significant increase in Bmax of [3H]PN 200-110 binding in diabetic rats depended on the duration of diabetes such that the increase was not found until 6 wk after STZ injection. An 8-wk intensive insulin treatment, which was initiated 2 wk after STZ injection, normalized the increase in [3H]PN 200-110 binding in STZ-D rats to control levels (85 +/- 4 fmol/mg protein). Furthermore, [3H]PN 200-110 binding to control cardiac membranes was dose-dependently inhibited in the presence of verapamil, a phenylalkylamine Ca2+ antagonist, but that was not the case in cardiac membranes isolated from STZ-D rats. These results indicate that voltage-sensitive Ca2+ channels in cardiac muscle isolated from STZ-D rats are quantitatively and qualitatively altered, because the course of diabetes and the increase in the channels can be prevented by treatment with insulin.
Diabetes 1990 Sep
PMID:Increase in [3H]PN 200-110 binding to cardiac muscle membrane in streptozocin-induced diabetic rats. 214 87

A 66-year-old female patient with a malignant insulinoma was treated with streptozotocin (STZ; Zanosar) in 5 cycles every 4 weeks as 5 day courses with an intravenous dosage of 850 mg per day. Under this treatment hypoglycemic episodes decreased continuously in number as well as severity and - after a delay of 12 months after the last treatment - an overt diabetes mellitus appeared. Plasma insulin concentrations dropped immediately after starting of STZ therapy. On the other hand, islet cell surface antibodies and their complement-dependent cytotoxicity increased continuously, being at their highest 6 months after termination of STZ treatment. Thus, STZ is able to induce a specific immune response against islet cells with a progressive damage of malignant insulin producing cells.
 ...
PMID:Autoimmune reactions in a patient with malignant insulinoma treated by multiple low dose streptozotocin. 215 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>