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

The present study was undertaken to determine how the responses to contractile agents are altered in aortas from rats with streptozotocin-induced diabetes and to explore the possible mechanisms of the altered responses in diabetes. Rats were given an intravenous injection of 45 mg/kg streptozotocin. Eight to 12 weeks after treatment, aortas were isolated and set up for measurement of isometric tension. Diabetic aortas exhibited significantly lesser contractions in response to high K+ than those from age-matched controls. Furthermore, the Ca2+ channel agonist Bay K 8644 was not able to consistently contract diabetic aortas even when they were partially depolarized by an elevation of the extracellular K+ concentration to 15 mM where the agonist produced concentration-dependent contractions in all control aortas. On the other hand, the contractile responses to norepinephrine, 5-hydroxytryptamine, endothelin-1 and U46619 were significantly enhanced in diabetic rat aortas. All of the enhanced responses of diabetic aortas were completely eliminated in the presence of the Ca2+ channel antagonist nifedipine. The contractile responses of aortas from both control and diabetic rats to these agonists were abolished or strongly inhibited by the protein kinase C inhibitor staurosporine, and no significant difference was found in the magnitude of the contractile responses of aortas between control and diabetic rats to the agonists in the presence of staurosporine. In diabetic aortas, the protein kinase C activators phorbol 12, 13-dibutyrate and 12-O-tetradecanoylphorbol 13-acetate elicited a delayed, sharply developing rise in tension following the initial, gradually developing contraction, while these agents produced only the initial, slowly developing contraction in control aortas. As a result, the contractions induced by phorbol esters were greater in diabetic aortas than in controls. The enhanced contractile responses of diabetic aortas to phorbol esters were not observed in Ca(2+)-free medium or in the presence of nifedipine. In Ca(2+)-free medium, the transient contraction induced by caffeine was significantly diminished in diabetic aortas, in contrast to the phasic contraction by norepinephrine which was similarly observed in control and diabetic aortas. These results indicate that the extracellular Ca(2+)-dependent contractions elicited by receptor activation are enhanced in aortas from diabetic rats, and this is presumably related to a greater influx of Ca2+ through transmembrane Ca2+ channels as a consequence of increased protein kinase C-activated processes. On the other hand, the contractions associated with depolarization-evoked activation of Ca2+ channels are diminished in diabetic aortas, possibly due to an alteration in activation of the channels by membrane depolarization, and Ca(2+)-induced Ca2+ release from intracellular stores appears to be impaired in diabetes.
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PMID:[Pharmacological studies on alterations in contractile reactivity in aortas isolated from experimental diabetic rats]. 946 17

Free Ca2+ was measured in intracellular stores of individual mouse pancreatic beta-cells using dual-wavelength microfluorometry and the low-affinity Ca2+ indicator furaptra. Controlled permeabilization of the plasma membrane with 4 micromol/l digitonin revealed that 22% of the furaptra was trapped in intracellular nonnuclear compartments. When 3 mmol/l ATP and 200 nmol/l Ca2+ were simultaneously present, this cation rapidly accumulated in the organelle pool, reaching an average concentration of 200-500 micromol/l. Whereas agents affecting the mitochondrial function (5 mmol/l succinate, 2 micromol/l ruthenium red, or 10 micromol/l antimycin A + 2 microg/ml oligomycin) had little effects, the Ca2+-ATPase inhibitor thapsigargin released 92% of the Ca2+ mobilizable with the ionophore Br-A23187. Digital imaging revealed regional differences in the organelle Ca2+. The regions with the highest Ca2+ concentration were particularly responsive to inositol 1,4,5-trisphosphate (IP3). IP3 mobilized Ca2+ in a dose-dependent way with half-maximal and maximal effects at about 1 and 5 micromol/l, respectively. High concentrations of IP3 released about half of the thapsigargin-sensitive Ca2+, but there were no responses to agents known to activate ryanodine receptors, such as 10 mmol/l caffeine, 0.1-1 micromol/l ryanodine, or 1-5 micromol/l cyclic ADP ribose. The results reinforce the concept that mobilization of intracellular Ca2+ in the pancreatic beta-cell is mediated by IP3 receptors rather than ryanodine receptors.
Diabetes 1998 Aug
PMID:In situ characterization of nonmitochondrial Ca2+ stores in individual pancreatic beta-cells. 970 21

Elevation of intracellular glucose within retinal vascular cells is believed to be an important causal factor in the development of diabetic retinopathy. The intracellular glucose concentration is regulated by both the rate of glucose metabolism and glucose transport. Because retinal hypoxia often precedes proliferative diabetic retinopathy, we have studied the regulation of the glucose transport system by hypoxia in cultured bovine retinal endothelial cells (BRECs). Because retinal ischemia is known to increase intracellular adenosine levels, which subsequently regulate hypoxia-inducible genes, such as vascular endothelial growth factor and erythropoietin, the role of adenosine and its receptor-mediated pathways has also been evaluated. Hypoxia (0.5% O2, 5% CO2, and 94.5% N2) stimulated GLUT1 mRNA expression in BRECs in a time-dependent manner with an 8.9 +/- 1.5-fold (P < 0.01) increase observed after 12 h. GLUT1 mRNA expression returned to baseline (1.4 +/- 0.3-fold of control) within 12 h after reinstitution of normoxia. N6-Cyclopentyl adenosine (adenosine A1 receptor agonist, Kd = 1 nmol/l) did not affect GLUT1 mRNA expression at concentrations up to 1 micromol/l, while 2-p-(2-carboxyethyl)-phenethyl-amino-5'-N-ethylcarboxamidoadenosine and 5'-(N-ethylcalboxamido)-adenosine (adenosine A2 receptor [A2R] agonists, Kd = 15 and 16 nmol/l, respectively) increased mRNA levels at concentrations as low as 10 nmol/l. Maximal stimulation was 2.3 +/- 0.2- and 2.1 +/- 0.2-fold, respectively (P < 0.01). The adenosine A2a receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) (Kd = 100 nmol/l for A2R) inhibited hypoxia-stimulated GLUT1 mRNA expression by 40 +/- 8% at 100 nmo/l. Hypoxia upregulated GLUT1 protein expression by 3.0 +/- 0.3-fold after 12 h (P < 0.01), but this response was attenuated by CSC (P < 0.05). Hypoxia increased glucose transport activity by 2.1 +/- 0.3-fold (P < 0.001) after 12 h, a response inhibited 65% by CSC (P < 0.01). A protein kinase A (PKA) inhibitor (H89, 20 micromol/l) suppressed hypoxia-induced GLUT1 mRNA expression by 42 +/- 9% (P < 0.01). These data suggest that hypoxia in BRECs upregulates glucose transport activity through an increase of GLUT1 expression that is partially mediated by adenosine, A2R, and the cAMP-PKA pathway.
Diabetes 1998 Sep
PMID:Hypoxia upregulates glucose transport activity through an adenosine-mediated increase of GLUT1 expression in retinal capillary endothelial cells. 972 38

Premenstrual syndrome (PMS) is a recurrent disorder that occurs in the luteal phase of the menstrual cycle. It is characterized by intense physical, psychologic, and behavioral changes that interrupt interpersonal relationships and disrupt the lives of affected women. Up to 40% of women of childbearing age have some form of PMS, and up to 10% have severe signs and symptoms. There are at least four types of PMS, each with its own constellation of signs and symptoms. Related illnesses or illnesses that need to be ruled out include diabetes mellitus, thyroid dysfunction, hypoglycemia, and primary and secondary dysmenorrhea. Difficulty in identifying the exact etiology of the disorder is documented. Diagnostic issues include confusion over exact signs and symptoms, differential diagnoses, pertinent laboratory data, careful history taking, and the importance of women recording a menstrual cycle history on a calendar. Recommended first-line treatments include a diet low in salt, fat, caffeine, and sugar; an aerobic exercise regimen; and stress reduction via changes in lifestyle.
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PMID:Premenstrual syndrome: diagnosis and intervention. 977 69

Obesity is characterised by pathophysiological defects affecting both sides of the energy balance equation. Individuals with a predisposition to obesity have impaired appetite control when diets are fat-rich and energy dense. They also exhibit a lower than expected resting metabolic rate (RMR). A low RMR, in concert with a sedentary lifestyle, contributes to a low total energy output, which may lead to obesity if continued over a period of years. A low metabolic rate seems to be genetically determined, and is partly caused by low sympathetic nervous system activity. Classical treatment programmes for obesity do not provide a satisfactory long-term outcome for the majority of patients. Patients who achieve only a small weight loss during dietary therapy, and have a tendency to weight regain, are characterised by lower energy expenditure, lower sympathetic activity, and a reduced ability to mobilise fat stores, compared with patients who are more successful at losing weight. It is reasonable to improve or normalise these traits by supporting the dietary approach with pharmacological manipulation of central and peripheral pathways. Agents which stimulate adrenergic neurons are particularly suitable because they offer mechanisms for inhibiting hunger and for stimulating energy expenditure, lipolysis and fat oxidation. Sympathomimetic compounds can reduce appetite and increase energy expenditure. Energy expenditure can be increased by 5-10% via stimulation of a combination of beta-adrenoceptors; beta3-adrenoceptors may predominate during chronic therapy. This increased energy expenditure increases the relative proportion of fat oxidation; as this is not fully compensated by increased energy intake, a negative energy balance occurs. This mechanism may be responsible for the long-term weight loss efficiency of agents like ephedrine/caffeine and sibutramine. Pharmacotherapy can be used to support short-term induction of weight loss or long-term weight maintenance. In the latter case, adrenergic agents enable a greater proportion of patients to maintain a satisfactory weight loss, compared with patients treated with conventional programmes alone. Pharmacotherapy which stabilises the size of fat stores at a lower level contributes indirectly to a pronounced improvement of risk factors, leading to a decreased potential for cardiovascular disease, type 2 diabetes and associated morbidity.
Exp Clin Endocrinol Diabetes 1998
PMID:What do pharmacological approaches to obesity management offer? Linking pharmacological mechanisms of obesity management agents to clinical practice. 979 79

The mechanism of the diminished inotropic response to beta-adrenoceptor stimulation in diabetic hearts was studied in enzymatically isolated diabetic rat ventricular myocytes in comparison with age-matched controls. The increases in contractions and intracellular Ca2+ concentration ([Ca2+]i) transients produced by isoproterenol were markedly diminished in diabetic myocytes. The inotropic and [Ca2+]i responses to forskolin and dibutyryl cAMP (DBcAMP) were also reduced. No significant difference was found in the stimulating effects of isoproterenol, forskolin, and DBcAMP on the L-type Ca2+ current (ICa) between control and diabetic myocytes. The rise of [Ca2+]i in response to rapid caffeine application, an index of sarcoplasmic reticulum (SR) Ca2+ content, was significantly decreased in diabetic myocytes. Isoproterenol, forskolin, and DBcAMP enhanced this [Ca2+]i response to caffeine in control myocytes more markedly than in diabetic myocytes. The changes in the isoproterenol responses observed in diabetic myocytes were prevented by insulin therapy. We conclude that 1) diabetes causes an impairment of the contractile and [Ca2+]i responses of cardiac myocytes when stimulated at both beta-adrenoceptors and the postreceptor level without affecting the ICa response and 2) altered SR functions of uptake and/or release of Ca2+ may primarily contribute to the diminished beta-adrenergic response.
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PMID:Effects of beta-adrenoceptor stimulation on contractility, [Ca2+]i, and Ca2+ current in diabetic rat cardiomyocytes. 984 12

Bone contains several growth factors, including bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-beta), insulin-like growth factors I and II (IGF-I and IGF-II), platelet derived growth factor (PDGF) and basic and acidic fibroblast growth factor (bFGF and aFGF). The BMPs are the only factors known to provoke bone formation heterotopically by making undifferentiated mesenchymal cells differentiate into osteoblasts (osteoinduction). Much of our knowledge of osteoinduction derives from studies in rodents of heterotopically implanted demineralised bone which contains various growth factors, including BMPs. This model has been used to examine the effect on osteoinduction of different factors, including the type of host soft tissue, age and species of donor and recipient, demineralisation procedure, storage and sterilisation procedures, experimental diabetes, dietary factors, hormones, growth factors, caffeine, biphosphonates, indomethacin and biomaterials. Demineralised bone enhances bone formation experimentally in various animal models, including cranio-maxillofacial reconstructions, healing of diaphyseal defects, and spinal fusion; demineralised bone has also been used in a limited way clinically. However, sufficient osteoinduction in humans may require a higher concentration of BMPs and other growth factors than those found in demineralised bone.
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PMID:Osteoinduction by demineralised bone. 991 41

Commercial, public foodservices are experiencing an increasing demand for menu selections consumers see as healthful. Demographic, economic and lifestyle forces are resulting in a growing proportion of individuals and families who eat away from home more frequently. Many are seeking prudent food choices not only at home, but also in foodservice operations. To them, nutrition represents one controllable lifestyle element which can influence their personal health. Weight control and preventive nutrition are the nutrition-related objectives of most consumers interested in foodservice nutrition. They look to dietary guidelines, both those which are specific to their particular health concerns, (e.g. weight control), and those intended as eating-style changes to reduce the risk of such diet-related conditions and diseases as obesity, atherosclerosis, high blood pressure, diabetes and certain forms of cancer. Focusing on these health objectives, interested foodservice operators should offer items which allow consumers to avoid certain foods and food preparation methods which add up to too much of the following: total calories; fat; refined carbohydrates; cholesterol; sodium; and certain controversial substances, (e.g., caffeine). They seek to replace some of the 'avoid' items with a variety of choices of minimally-processed plant foods, and with less-fatty animal foods. Employee education to support menuing nutrition should begin with the development of an awareness of specific target market health concerns. Employees can then be made familiar with methods to translate these dietary wants and needs into appealing, well-tuned products and service elements. The success of nutrition program elements relies heavily on this understanding by employees in their roles from recipe development to table service.
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PMID:Commercial foodservice considerations in providing consumer-driven nutrition program elements. Part I. Consumer health objectives and associated employee education needs. 1029 82

Depressed myofibrillar Ca2+-ATPase activity and sarcoplasmic reticulum (SR) Ca2+ uptake are important mechanisms that are responsible for the cardiac dysfunction exhibited by insulin-deficient (type I) diabetic animals. The JCR:LA-cp rat is a model for type II non-insulin-dependent diabetes mellitus (NIDDM). This rat is insulin resistant, obese, and has high levels of circulating glucose, cholesterol, insulin, and triglycerides. The purpose of this study was to determine whether changes in cardiac myofibrillar, SR, and cardiomyocyte function exist in this model of type II diabetes. Myofibrils and SR were isolated from hearts by differential centrifugation. Surprisingly, we found that myofibrillar Ca2+-ATPase activities were unaltered in these animals. Ca2+ uptake in isolated SR fractions was increased in diabetic cp/cp rats, whereas Ca2+-ATPase activity and ryanodine binding were unchanged. Cardiomyocytes isolated from hearts of control and experimental animals had similar active cell shortening and intracellular Ca2+ concentration under basal conditions and in response to caffeine. Our data argue against the presence of a cardiomyopathy in this diabetic model and suggest that insulin may be an important factor in the cardiomyopathy observed in type I diabetic models.
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PMID:Cardiac myofibrillar and sarcoplasmic reticulum function are not depressed in insulin-resistant JCR:LA-cp rats. 1036 58

This study was designed in order to gain insight into possible changes in the inward sodium-calcium exchange current (INa-Ca) and the L-type calcium current (ICa), in ventricular myocytes isolated from streptozotocin-induced diabetic rats. Recordings were made using the nystatin-perforated patch technique which minimizes interference with the normal intracellular Ca2+ buffering mechanisms. The averaged INa-Ca current density elicited by Ca2+ current was smaller in diabetic than in normal myocytes at all potentials tested. INa-Ca activated by rapid application of caffeine was significantly reduced and the decay phase was prolonged. The density of ICa was also significantly reduced by diabetes in the range of test potentials between -10 and +50 mV. In addition, the fast time constant of ICa inactivation, which represents mainly the sarcoplasmic reticulum (SR) Ca2+ release-induced inactivation, was significantly higher in diabetic than in normal myocytes. The decrease in ICa, which is the main source of trigger Ca2+ for SR Ca2+ release, may explain the significantly lowered peak systolic [Ca2+]i previously shown in diabetic myocytes. As activation of ICa is essential for subsequent stimulation of INa-Ca, reduced ICa may contribute to decreasing activation of the Na+-Ca2+ exchanger.
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PMID:Decrease in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes. 1038 93


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