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

Metabolic Syndrome (MetS) represents a constellation of markers that indicates a predisposition to diabetes, cardiovascular disease and other pathologic states. The definition and treatment are a matter of current debate and there is not general agreement on a precise definition or, to some extent, whether the designation provides more information than the individual components. We consider here five indicators that are central to most definitions and we provide evidence from the literature that these are precisely the symptoms that respond to reduction in dietary carbohydrate (CHO). Carbohydrate restriction is one of several strategies for reducing body mass but even in the absence of weight loss or in comparison with low fat alternatives, CHO restriction is effective at ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG), low HDL and high blood pressure. In addition, low fat, high CHO diets have long been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen glycemic control. Thus, whereas there are numerous strategies for weight loss, a patient with high BMI and high TAG is likely to benefit most from a regimen that reduces CHO intake. Reviewing the literature, benefits of CHO restriction are seen in normal or overweight individuals, in normal patients who meet the criteria for MetS or in patients with frank diabetes. Moreover, in low fat studies that ameliorate LDL and total cholesterol, controls may do better on the symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful phenomenon and may, in fact, be operationally defined as the set of markers that responds to CHO restriction. Insofar as this is an accurate characterization it is likely the result of the effect of dietary CHO on insulin metabolism. Glucose is the major insulin secretagogue and insulin resistance has been tied to the hyperinsulinemic state or the effect of such a state on lipid metabolism. The conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.
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PMID:Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. 1628 55

Dopamine, via activation of D1-like receptors, inhibits Na,K-ATPase and Na,H-exchanger in renal proximal tubules and promotes sodium excretion. This effect of dopamine is not seen in conditions associated with oxidative stress such as hypertension, diabetes, and aging due to uncoupling of D1-like receptors from G proteins. To identify the role of oxidative stress in uncoupling of the D1-like receptors, we utilized primary cultures from rat renal proximal tubules. Hydrogen peroxide (H2O2), an oxidant, treatment to the cell cultures increased the level of malondialdehyde, a marker of oxidative damage. Further, H2O2 decreased membranous D1-like receptor numbers and proteins, D1-like agonist (SKF 38393)-mediated [35S]GTPgammaS binding and SKF 38393-mediated inhibition of Na,K-ATPase. Moreover, H2O2 treatment to the cultures caused membranous translocation of G-protein-coupled receptor kinase 2 (GRK 2) and increased serine phosphorylation of D1A receptors accompanied by an increase in protein kinase C (PKC) activity. Interestingly, PKC inhibitors blocked the H2O2-mediated stimulation of GRK 2 and serine phosphorylation of D1A receptors. Further, GRK 2 antisense but not scrambled oligonucleotides attenuated the effect of H2O2 on membranous expression of GRK 2. Moreover, direct activation of PKC with phorbol ester (PMA) resulted in reduction of SKF 38393-mediated [35S]GTPgammaS binding. We conclude that H2O2 stimulates PKC leading to the activation of GRK 2, which causes serine phopshorylation of D1A receptors and receptor G-protein uncoupling in these cells, resulting in impairment in D1-like receptor function.
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PMID:Hydrogen peroxide causes uncoupling of dopamine D1-like receptors from G proteins via a mechanism involving protein kinase C and G-protein-coupled receptor kinase 2. 1633 75

The present study investigated the dietary effect of conjugated linolenic acid (CLnA) on lipid profiles and lipid peroxidations in alloxan-induced diabetes mellitus in rats. Diabetic rats were fed with 20% sunflower oil (diabetic control), sunflower oil supplemented with 0.5% CLnA, sunflower oil supplemented with 0.15% alpha-tocopherol, and sunflower oil containing 0.25% CLnA + 0.15% alpha-tocopherol. The results demonstrated that 0.5% CLnA, 0.15% alpha-tocopherol, and 0.25% CLnA + 0.15% alpha-tocopherol each on supplementation significantly lowered total cholesterol and non-HDL-cholesterol in comparison with the diabetic control group. The TAG level was significantly lowered in both the 0.15% alpha-tocopherol and 0.25% CLnA + 0.15% alpha-tocopherol groups. LDL-lipid peroxidation and erythrocyte membrane lipid peroxidation were reduced significantly in each of the experimental groups vs. the control group. The CLnA + alpha-tocopherol diet induced a greater reduction in membrane lipid and liver lipid peroxidation than the alpha-tocopherol diet alone. In conclusion, dietary CLnA exerts antioxidant activity as evidenced by reduced lipid peroxidation in chemically induced diabetes mellitus.
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PMID:Dietary comparison of conjugated linolenic acid (9 cis, 11 trans, 13 trans) and alpha-tocopherol effects on blood lipids and lipid peroxidation in alloxan-induced diabetes mellitus in rats. 1655 71

Oxidative stress plays a major role in the pathogenesis and in the onset of macrovascular complications of diabetes. We previously reported that the antihyperglycaemic drug metformin was able to decrease significantly intracellular reactive oxygen species (ROS) production of bovine aortic endothelial cells (BAEC) activated by high levels of glucose and angiotensin II (ANG). The aim of the present study was to investigate whether the antioxidant effect of metformin on BAEC could be mediated through a modulation of protein kinase C (PKC) activity, which plays a key role in the pathophysiology of diabetes. The effects of metformin on intracellular ROS production, PKC translocation and activity were studied on endothelial cells stimulated by PMA (a direct PKC activator), ANG or high levels of glucose as pathophysiological stimuli of endothelial dysfunction in diabetes. We showed that metformin decreased ROS production on PMA-, ANG- and glucose-stimulated BAEC in a similar manner to that obtained by PKC specific inhibitors (calphostin C, chelerythrine) alone. On the other hand, metformin reduced both PKC membrane translocation and kinase activity in ANG-stimulated cells. In PMA-activated cells, metformin reduced membrane PKC activity but we did not observe any alteration of PKC membrane translocation. Finally, in vitro incubation with purified PKC indicated that metformin had no direct effect on PKC activity. Taken together, our results suggest that metformin exerted intracellular antioxidant properties by decreasing ROS production through the inhibition of PKC activity.
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PMID:Metformin reduces angiotensin-mediated intracellular production of reactive oxygen species in endothelial cells through the inhibition of protein kinase C. 1673 Jun 66

The predisposition to infection and chronic inflammation in diabetes may in part be related to the effects of hyperglycemia or other metabolic abnormality on polymorphonuclear leukocytes (PMN). We evaluated oxidative respiratory burst activity (superoxide production) in non-stimulated and stimulated PMN from 70 stable type 2 Hispanic diabetic patients, as compared to 70 healthy Hispanic individuals without diabetes. The influences of protein kinase C (PKC) inhibitors and certain antibiotics on superoxide production were examined. Both resting and stimulated (PMA, zymosan) PMN from diabetic individuals produced more superoxide than PMN from controls. Inhibitors of PKC, a possible mediator of the augmented respiratory burst activity, decreased superoxide production in all (resting and stimulated) diabetic and control PMN. Azithromycin, which is markedly concentrated by PMN, profoundly inhibited superoxide generation in all groups of diabetic and control cells. PMN from Hispanic diabetic patients produced greater quantities of superoxide than non-diabetic controls. This increased oxidative respiratory burst activity may predispose to infection and chronic inflammation in diabetes. PKC inhibitors and azithromycin inhibited this respiratory burst response. The possible role of PKC (especially PKC beta) as the mediator of this augmented respiratory burst response requires further evaluation, and may lead to therapeutic studies with appropriate inhibitors.
Diabetes Res Clin Pract 2007 Apr
PMID:Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes. 1695 66

Vanadium(IV) oxo-bis(maltolato) (BMOV), an organovanadium compound, is a potent insulinomimetic agent and improves glucose homeostasis in various models of diabetes. We have shown previously that BMOV stimulates the phosphorylation of PKB which may contribute as one of the mechanisms for the insulinomimetic effect of this compound. However, the upstream mechanism of BMOV-induced PKB phosphorylation remains elusive. Therefore, in this study, we examine the upstream events leading to BMOV-induced PKB phosphorylation in HepG2 cells. Since BMOV is an inhibitor of protein tyrosine phosphatases and through enhanced tyrosine phosphorylation may activate various protein tyrosine kinases (PTK), we have investigated the potential role of different receptor or nonreceptor PTK in mediating BMOV-induced PKB phosphorylation. Among several pharmacological inhibitors that were tested, only AG1024, a selective inhibitor of IGF-1R-PTK, almost completely blocked BMOV-stimulated phosphorylation of PKB. In contrast, AG1295 and AG1478, specific inhibitors of PDGFR and EGFR, respectively, were unable to block the BMOV response. Moreover, efficient reduction of the level of IGF-1R protein expression by antisense oligonucleotides (ASO) attenuated BMOV-induced PKB phosphorylation. BMOV-induced PKB phosphorylation was associated with an increased level of tyrosine phosphorylation of the IRbeta subunit, IGF-1Rbeta subunit, IRS-1, and p85alpha subunit of PI3-kinase. However, this response was independent of IR-PTK activity because in cells overexpressing a PTK-inactive form of IR, insulin response was attenuated while the effect of BMOV remained intact. A role of PKC in BMOV-induced response was also tested. Pharmacological inhibition with chelerythrine, a nonselective PKC inhibitor, or rottlerin, a PKCdelta inhibitor, as well as chronic treatment with PMA attenuated BMOV-induced PKB phosphorylation. In contrast, GO6976 and RO31-8220 PKCalpha/beta selective inhibitors failed to alter the BMOV effect. Taken together, these data suggest that IGF-1R and PKCdelta are required to stimulate PKB phosphorylation in response to BMOV in HepG2 cells and provide new insights into the molecular mechanism by which this compound exerts its insulinomimetic effects.
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PMID:Involvement of insulin-like growth factor type 1 receptor and protein kinase Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase B in HepG2 cells. 1698 20

The metabolic syndrome represents a summation of obesity-driven risk factors for atherosclerotic CVD and type 2 diabetes. Definitions of the syndrome vary but in general agree closely in identifying subjects. The relationships between the metabolic syndrome and atherosclerotic CVD and diabetes also vary, with relative risks of approximately 1.5-3.0 and approximately 3.0-5.0 respectively. Insulin resistance appears to explain much of the pathophysiology of the syndrome. Both increased fatty acid flux and an excess of circulating pro-inflammatory cytokines are likely mediators. With increased waist circumference, increases in fatty acid delivery to the liver result in higher rates of hepatic glucose production and increases in the secretion of apoB-containing lipoproteins. Concomitant changes in HDL ensue, including a replacement of the cholesterol content with TAG, an accelerated clearance from the plasma and thus a reduced number of HDL particles. Typically also present are increases in small dense LDL. Hypertension in part relates to the insulin resistance, but may involve other mechanisms. Impaired fasting glucose often relates to defects in insulin secretion in addition to insulin resistance, and probably more than any other component of the syndrome predicts the increased incidence of type 2 diabetes. Although not included in the diagnostic criteria, increases in pro-inflammatory cytokines and pro-thrombotic factors, in addition to decreases in plasma adiponectin, may also contribute to the increased incidence of atherosclerotic CVD and diabetes. In general, the greater the number of metabolic syndrome components, the greater the risk for these outcomes. The cytokines and pro-thrombotic factors also appear to contribute.
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PMID:Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD. 1734 75

Obesity resides upstream of the constituents of metabolic syndromes such as diabetes, hypertension, hyperlipidemia, and arteriosclerosis. Postprandial hyperlipidemia is also implicated in atherogenesis. Therefore, factors that influence the body adiposity and the magnitude of postprandial hyperlipidemia have been intensively investigated. Diacylglycerol (DAG) oil, which is defined to contain DAG 80% (w/w) or greater in the present presentation, is an edible oil with similar taste and usability compared with conventional edible oil rich in TAG. Safety of DAG has been widely evaluated and listed as a GRAS (Generally Recognized as Safe) substance by US FDA. The aim of this review was to summarize the metabolism and nutritional functions of DAG based on the data from scientific journals and conference publications. Effect of DAG ingestion on postprandial elevations of serum lipids was investigated in several dosages, food formula, and in subjects in various conditions. Postprandial triglyceride in serum and the chylomicron fraction are significantly smaller after DAG consumption compared with TAG with a similar fatty acid composition in healthy subjects, and was remarkably reduced in subjects with insulin resistance. Long-term DAG ingestion in controlled diet or free-living condition significantly decreased body adiposity and improved type II diabetic complications. A single dose DAG consumption significantly increased fat oxidation as compared to eucaloric TAG ingestion. DAG oil consumption might be beneficial in reducing the risk factors for lifestyle-related diseases such as obesity, visceral obesity, postprandial hyperlipidemia, insulin resistance, and atherosclerosis.
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PMID:Metabolism of diacylglycerol in humans. 1739 38

A high concentration of dietary carbohydrate is suggested to increase the risk of obesity and diabetes mellitus in domestic cats. To evaluate this, food intake, body weight, fat mass and circulating adiposity-related factors were determined in twenty-four sexually mature (9-12 months) cats assigned to four six-cat dietary groups balanced for body weight and sex. The effect of dietary fat in exchange for carbohydrate at 9, 25, 44 and 64 % of metabolisable energy (ME) in a purified diet of constant protein:ME ratio was studied 13 weeks before and 17 weeks after gonadectomy (GX). Body weight did not significantly change among the cats before GX except for an increase of 17 (sem 5) % in cats given the highest-fat diet. Following GX, all groups gained body weight, and body fat mass was positively correlated (r 0.50; P < 0.04) with dietary fat percentage. Post-GX weight gains were much greater for females (+39 (sem 5) %) than males (+10 (sem 4) %). Plasma ghrelin concentration negatively correlated (P < 0.02) with dietary fat percentage and, before GX, was greater (P < 0.05) in females than males. Plasma insulin concentration increased with weight gain induced by high dietary fat. Plasma glucose, TAG and leptin concentrations were not affected by dietary fat percentage, GX or weight gain. These data provide evidence that in cats, high dietary fat, but not carbohydrate, induces weight gain and a congruent increase in insulin, while GX increases sensitivity to weight gain induced by dietary fat.
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PMID:Gonadectomy and high dietary fat but not high dietary carbohydrate induce gains in body weight and fat of domestic cats. 1752 82

The improved effects of dietary chickpeas on visceral adiposity, dyslipidaemia and insulin resistance were examined. Rats were fed a normal-fat diet (NFD), a high-fat diet (HFD) or a high-fat plus chickpea diet (HFD+CP) for 8 months. The epididymal fat pad weight v. total body weight of rats was higher in the HFD group (0.032 (sd 0.0042) g/g) than in the NFD group (0.015 (sd 0.0064) g/g) and smaller in the HFD+CP group (0.023 (sd 0.0072) g/g) compared with the HFD group (P < 0.05). Chickpea treatment also induced a favourable plasma lipid profile reflecting decreased TAG, LDL-cholesterol (LDL-C) and LDL-C:HDL-cholesterol levels (P < 0.05). HFD-fed rats had higher TAG concentration in muscle and liver, whereas the addition of chickpeas to the HFD drastically lowered TAG concentration (muscle, 39 %; liver, 23 %). The activities of lipoprotein lipase (LPL) in epididymal adipose tissue and hepatic TAG lipase in liver recorded a 40 and 23 % increase respectively in HFD rats compared with those in NFD rats; dietary chickpeas completely normalised the levels. Furthermore, chickpea-treated obese rats also showed a markedly lower leptin and LPL mRNA content in epididymal adipose tissue. An insulin tolerance test, oral glucose tolerance test and insulin-releasing test showed that chickpeas significantly improved insulin resistance, and prevented postprandial hyperglycaemia and hyperinsulinaemia induced by the chronic HFD. The present findings provide a rational basis for the consumption of chickpeas as a functional food ingredient, which may be beneficial for correcting dyslipidaemia and preventing diabetes.
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PMID:Dietary chickpeas reverse visceral adiposity, dyslipidaemia and insulin resistance in rats induced by a chronic high-fat diet. 1766 45


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