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 authors performed the study of the influence of spa treatment in Wysowa Health Resort on heart function in 294 subjects during their 24-day stay in sanatorium within three groups of patients: 28 with diabetes mellitus, 63 with arterial hypertension and a control group. Hemodynamic parameters were recorded by non-invasive impedance cardiography twice: in the first three days of spa treatment and again in the last three days of a 24-day stay. The following hemodynamic parameters were evaluated: SBP, DBP, MAP, CI, SVRI, IC, ACI, LCWI, EF, SI, EDI, TFC, HR. Relation of hemodynamic parameter changes on other measurable features was described in each group by correlation analysis. A small value of Pearson r coefficient proves a small relation among the examined variables. Both in the control group and in diabetic patients and also in patients with arterial hypertension, a spa treatment in Wysowa Health Resort does not show a significant influence to the examined hemodynamic parameters measured by impedance cardiography.
 ...
PMID:[The influence of the Wysowa Spa treatment on heart function]. 1049 25

The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily of cell surface molecules, interacts with distinct molecules implicated in homeostasis, development and inflammation, and certain diseases such as diabetes and Alzheimer's disease. Engagement of RAGE by a ligand triggers activation of key cell signalling pathways, such as p21ras, MAP kinases, NF-kappaB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin, a polypeptide linked to outgrowth of cultured cortical neurons derived from developing brain. Indeed, the co-localization of RAGE and amphoterin at the leading edge of advancing neurites indicated their potential contribution to cellular migration, and in pathologies such as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin decreased growth and metastases of both implanted tumours and tumours developing spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases; molecular effector mechanisms importantly linked to tumour proliferation, invasion and expression of matrix metalloproteinases.
 ...
PMID:Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. 1083 Sep 43

Changes in cell hydration are critically important for the signalling towards metabolic responses to hormones, substrates and reactive oxygen intermediates. In liver insulin-induced cell swelling is due to a net K(+)-uptake resulting from the concerted activation of Na(+)/K(+)/2Cl(-) cotransport, Na(+)/H(+) exchange and the Na(+)/K(+)-ATPase. Insulin-induced swelling is essential for generating the antiproteolytic response to the hormone, which depends on activation of the MAP-kinase p38. Recent investigations show, that cell swelling induced by either hypoosmolarity or insulin triggers the activation of signalling cascades. Cell swelling by insulin is Ptdins-3-kinase mediated and contributes to the activation of Erk- and p38-type MAP-kinases. Conditions dehydrating insulin target tissues such as hyperosmolarity or amino acid deprivation are frequently associated with insulin resistance. In liver, hyperosmolarity impairs the Ptdins-3-kinase-dependent K(+) uptake and cell swelling in response to insulin, leading to resistance of MAP-kinases and proteolysis to regulation by insulin. Likewise, a reduction of insulin-induced swelling by the loop diuretics furosemide and bumetanide cause insulin resistance shown by the levels of cell swelling, MAP-kinase activation and proteolysis control. Blockage of the cell volume response to insulin may be the common denominator in dehydration-induced insulin resistance found in clinical settings such as sepsis, burn injury and diabetes mellitus.
 ...
PMID:Cell hydration and insulin signalling. 1112 22

Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state.
 ...
PMID:Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study. 1120 Mar 6

Protein kinase C (PKC) is a family of multifunctional isoenzymes, activated by diacylglycerols (DAGs), which play a central role in signal transduction and intracellular crosstalk by phosphorylating at serine/threonine residues an array of substrates, including cell-surface receptors, enzymes, contractile proteins, transcription factors and other kinases. Individual isozymes vary in their pattern of tissue and subcellular distribution, function and Ca2+/phospholipid cofactor requirements, and in diabetes there is widespread activation of the DAG-PKC pathway in metabolic, cardiovascular and renal tissues. In liver, muscle and adipose tissue, PKC isozymes have been implicated both as mediators and inhibitors of insulin action. Activation of DAG-sensitive PKC isoforms, such as PKC-theta and PKC-epsilon, down-regulates insulin receptor signalling and could be an important biochemical mechanism linking dysregulated lipid metabolism and insulin resistance in muscle. On the other hand, atypical PKC isozymes, such as PKC-zeta and PKC-lambda, have been identified as downstream targets of PI-3-kinase involved in insulin-stimulated glucose uptake, especially in adipocytes. Glucose-induced de novo synthesis of (palmitate-rich) DAG and sustained isozyme-selective PKC activation (especially but not exclusively PKC-beta) has been strongly implicated in the pathogenesis of diabetic microangiopathy and macroangiopathy through a host of undesirable effects on endothelial function, VSM contractility and growth, angiogenesis, gene transcription (in part by MAP-kinase activation) and vascular permeability. Interventions that increase DAG metabolism (e. g. vitamin E) and/or inhibit PKC isozymes (e. g. the beta-selective inhibitor LY333531) ameliorate the biochemical and functional consequences of DAG-PKC activation in experimental diabetes, for example improving retinal blood flow and albuminuria in parallel with reductions in membrane-associated PKC isozyme activities. Thus, a greater understanding of the functional diversity and pathophysiological regulation of PKC isozymes is likely to have important clinical and therapeutic benefits.
 ...
PMID:Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. 1144 Mar 58

Troglitazone (TRO) and rosiglitazone (RSG) belong to the thiazolidinedione class (insulin-sensitizing agents) and exert many of their metabolic effects as peroxisome proliferator-activated receptor gamma (PPARgamma) ligands. In the present study we examined the effects of TRO and RSG on LDL-induced VSMC growth. Pretreatment of VSMC with 1 microM TRO or 0.1 microM RSG completely blocked the LDL-induced cell proliferation as measured by [3H]thymidine incorporation into DNA and by determination of the cell number. We then examined with Western blotting whether these growth suppressing effects are mediated through the mitogen-activated protein kinase (MAPK) pathway, a common signaling pathway activated by growth factors. TRO and RSG had no effect on the LDL-induced stimulation of the MAP kinases ERK1/2, p38 and SAP/JNK. We conclude that thiazolidinediones are potent inhibitors of LDL-induced VSMC growth acting downstream of the cytoplasmic activation of MAPK.
Exp Clin Endocrinol Diabetes 2001
PMID:Troglitazone and rosiglitazone inhibit the low density lipoprotein-induced vascular smooth muscle cell growth. 1145 32

We compared the relations of 4 blood pressure (BP) indexes (pulse pressure [PP], systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure [MAP]) with 25-year mortality rates for coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in younger, middle-aged, and older men and women by using data from a long-term prospective epidemiological study of employed persons who were screened between 1967 and 1973. A single supine BP measurement was obtained at baseline. Vital status was determined through 1995. We report on 5 groups (total, 28 360 participants) consisting of men age 18 to 39, 40 to 59, and 60 to 74 years and of women age 40 to 59 and 60 to 74 years who were not receiving antihypertensive treatment, had no history of CHD, and did not have diabetes. Cox proportional hazards analyses were used to determine multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index; Wald chi(2) tests were used to compare the strength of relations. Relations of PP were less strong than were those of SBP for all end points in all age/gender groups. SBP or MAP showed the strongest relations to all end points in all age/gender groups (hazard ratio, 1.17 to 1.36). The relations of SBP to death were stronger than were those of DBP, except for middle-aged men and for CVD in women. DBP showed significant positive associations with death, after control for SBP, in middle-aged participants. In conclusion, these data indicate that the long-term risk of high BP should be assessed mainly on the basis of SBP or of SBP and DBP together, not on the basis of PP, in apparently healthy adults.
 ...
PMID:Pulse pressure compared with other blood pressure indexes in the prediction of 25-year cardiovascular and all-cause mortality rates: The Chicago Heart Association Detection Project in Industry Study. 1184 4

If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.
 ...
PMID:Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies. 1151 86

Insulin induces a broad spectrum of effects over a wide time interval. It also stimulates the phosphorylation of some cellular proteins, while decreasing the state of phosphorylation of others. These observations indicate the presence of different, but not necessarily mutually exclusive, pathways of insulin action. One well-known pathway represents a phosphorylation cascade initiated by the tyrosine kinase activity of the insulin receptor followed by involvement of different MAP-kinases. Another pathway suggests the existence of low molecular weight insulin mediators whose synthesis and/or release is initiated by insulin. Comparable analysis of two kinds of insulin mediators, namely inositolphosphoglycans and prostaglandylinositol cyclic phosphate (cPIP), has been carried out. It has been shown that the expression of a number of enzymes, such as phospholipase A(2), phospholipase C, cyclo-oxygenase and IRS-1-like enzyme, could regulate the biosynthesis of cPIP in both normal and diabetes-related conditions. Data on the activity of a key enzyme of cPIP biosynthesis termed cPIP synthase (IRS-1-like enzyme) in various monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. It has been concluded that in vivo insulin increases cPIP synthase activity in both liver and subcutaneous adipose tissue of lean normal monkeys. It has been also suggested that abnormal production of cPIP could be related to several pathologies including glucocorticoid-induced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understanding of insulin action.
Diabetes Metab Res Rev
PMID:Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger of insulin action. Comparative analysis of two kinds of "insulin mediators". 1154 11

RAGE (receptor for advanced glycation end products) is a multiligand cell surface molecule of the immunoglobulin superfamily. It was originally described as a receptor for protein adducts formed by glycoxidation (AGEs) that accumulate in diseases such as diabetes and renal failure. Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. Moreover, Caco-2 cells were incubated in the presence of AGEs. Since RAGE ligation triggers the p21(ras) signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE N(epsilon)-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation.
 ...
PMID:RAGE expression and AGE-induced MAP kinase activation in Caco-2 cells. 1170 25


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