The Experts below are selected from a list of 6957 Experts worldwide ranked by ideXlab platform
Paul Ernsberger - One of the best experts on this subject based on the ideXlab platform.
-
Lipid-lowering actions of imidazoline antihypertensive agents in Metabolic Syndrome X
Naunyn-Schmiedeberg's archives of pharmacology, 2006Co-Authors: Rodney A. Velliquette, Rachel Kossover, Stephen F. Previs, Paul ErnsbergerAbstract:Agonists active at I1-imidazoline receptors (I1R) not only lower blood pressure but also ameliorate glucose intolerance, insulin resistance, and hyperlipidemia with long-term treatment. We sought to determine the possible mechanism for the lipid-lowering actions of imidazolines in a model of Metabolic Syndrome X, the spontaneously-hypertensive obese (SHROB) rat. The acute actions of moXonidine and rilmenidine, selective I1R agonists, were compared to a specific alpha2-adrenergic receptor agonist, guanabenz, with and without selective receptor blockers. MoXonidine and rilmenidine rapidly reduced plasma triglyceride (20+/-4% and 21+/-5%, respectively) and cholesterol (29+/-9% and 27+/-9%). In contrast, the specific alpha2-adrenergic receptor agonist guanabenz failed to reduce plasma lipids. Blocking eXperiments showed that moXonidine's actions were mediated by I1R and not alpha2-adrenergic receptors. To evaluate a hepatic site of action, radioligand binding studies with liver plasma membranes confirmed the presence of I1R. Intraportal moXonidine reduced plasma triglycerides by 23+/-3% within 10 min. MoXonidine inhibited hepatic triglyceride secretion by 75% compared to vehicle treatment. Tracer studies with 2H2O suggested that moXonidine inhibits de novo fatty acid synthesis. Thus, activation of I1R lowers plasma lipids, with the main site of action probably within the liver to reduce synthesis and secretion of triglycerides. More selective I1R agonists might provide monotherapy for hyperlipidemic hypertension.
-
Therapeutic actions of an insulin receptor activator and a novel peroXisome proliferator-activated receptor γ agonist in the spontaneously hypertensive obese rat model of Metabolic Syndrome X
The Journal of pharmacology and experimental therapeutics, 2005Co-Authors: Rodney A. Velliquette, Jacob E. Friedman, Jianhua Shao, Bei B. Zhang, Paul ErnsbergerAbstract:Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as Metabolic Syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroXisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoXy-2-propylphenoXy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of Syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg X min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold eXcess fasting insulin and increased insulin AUC (6300 ng X min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with Metabolic Syndrome but via distinct mechanisms.
-
The Role of I1-Imidazoline Receptors and a2-Adrenergic Receptors in the Modulation of Glucose and Lipid Metabolism in the SHROB Model of Metabolic Syndrome X
Annals of the New York Academy of Sciences, 2003Co-Authors: Richard J. Koletsky, Rodney A. Velliquette, Paul ErnsbergerAbstract:Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as Metabolic Syndrome X. With the notable eXception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of Metabolic Syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moXonidine have miXed effects on components of Metabolic Syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of Metabolic Syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moXonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moXonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moXonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.
-
The Role of I1-Imidazoline and α2-Adrenergic Receptors in the Modulation of Glucose Metabolism in the Spontaneously Hypertensive Obese Rat Model of Metabolic Syndrome X
The Journal of pharmacology and experimental therapeutics, 2003Co-Authors: Rodney A. Velliquette, Paul ErnsbergerAbstract:We eXamined glucose metabolism after I 1 -imidazoline (I 1 R) and α 2 -adrenergic receptor (α 2 AR) activation in an animal model of Metabolic Syndrome X. Fasted spontaneously hypertensive obese rats (SHROB) were given the I 1 R/α 2 AR agonists moXonidine and rilmenidine or the α 2 AR agonist guanabenz. Because of the dual specificity of moXonidine, its actions were split into adrenergic and nonadrenergic components by using selective antagonists: rauwolscine (α 2 AR) efaroXan (I 1 R/α 2 AR), or 2-endo-amino-3-eXo-isopropylbicyclo[2.2.1.]heptane (AGN 192403) (I 1 R). Hyperglycemia induced by moXonidine, rilmenidine, and guanabenz resulted from inhibition of insulin secretion. Similar responses were observed after oral dosing and in lean littermates. Glucagon was reduced by the I 1 R agonists (moXonidine, 32 ± 5%; rilmenidine, 24 ± 7%) but elevated by guanabenz (71 ± 32%). The hyperglycemic and hypoinsulinemic responses to moXonidine were blocked by rauwolscine. In contrast, rauwolscine potentiated the reduction in glucagon (39 ± 6%). AGN 193402 blocked the glucagon response without affecting hyperglycemia and hypoinsulinemia. EfaroXan blocked all responses to moXonidine. When SHROB rats were treated with moXonidine 15 min before an oral glucose tolerance test, the glucose area under the curve (AUC) was increased. Antagonizing the α 2 AR component of moXonidine9s action with rauwolscine improved glucose AUC 3-fold and facilitated the insulin secretory response and reduced glucagon secretion. Testing fasting glucose and insulin during 3 weeks of oral moXonidine revealed early hyperglycemia that later faded, and a progressive drop in fasting insulin. The acute hyperglycemia and hypoinsulinemia elicited by moXonidine and rilmenidine was mediated by α 2 AR, whereas I 1 R may reduce glucagon and increase insulin, particularly after a glucose load.
-
Plasma glucagon and free fatty acid responses to a glucose load in the obese spontaneous hypertensive rat (SHROB) model of Metabolic Syndrome X.
Experimental biology and medicine (Maywood N.J.), 2002Co-Authors: Rodney A. Velliquette, Richard J. Koletsky, Paul ErnsbergerAbstract:Metabolic Syndrome X is a cluster of abnormalities including insulin resistance, hyperlipidemia, hypertension, and obesity. We sought to determine if eXcess plasma glucagon and free fatty acids (FFA) might contribute to the insulin resistance in the obese spontaneous hypertensive rat (SHROB), a unique animal model of leptin resistance and Metabolic Syndrome X. SHROB were eXtremely hyperinsulinemic and mildly glucose intolerant compared with lean SHR. SHROB had elevated fasting plasma glucagon and FFA, and showed paradoXical responses to an oral glucose challenge, with increased glucagon at 30 and 60 min postchallenge (200% ± 45% and 91% ± 13%, respectively; n = 9). In lean SHR, glucagon was nearly unchanged by glucose loading ( 0.05; n = 5). Plasma FFA were not affected by a glucose load in SHROB, whereas SHR showed a decrease of 40% ± 6% (n = 5–9). The I/G molar ratio changed in opposite directions in the two genotypes, with a decrease in SHROB at 30 and 60 min, in contrast to the appro...
Undurti N. Das - One of the best experts on this subject based on the ideXlab platform.
-
Gene eXpression profile in obesity and type 2 diabetes mellitus.
Lipids in health and disease, 2007Co-Authors: Undurti N. Das, Allam Appa RaoAbstract:Obesity is an important component of Metabolic Syndrome X and predisposes to the development of type 2 diabetes mellitus. The incidence of obesity, type 2 diabetes mellitus and Metabolic Syndrome X is increasing, and the cause(s) for this increasing incidence is not clear. Although genetics could play an important role in the higher prevalence of these diseases, it is not clear how genetic factors interact with environmental and dietary factors to increase their incidence. We performed gene eXpression profile in subjects with obesity and type 2 diabetes mellitus with and without family history of these diseases. It was noted that genes involved in carbohydrate, lipid and amino acid metabolism pathways, glycan of biosynthesis, metabolism of cofactors and vitamin pathways, ubiquitin mediated proteolysis, signal transduction pathways, neuroactive ligand-receptor interaction, nervous system pathways, neurodegenerative disorders pathways are upregulated in obesity compared to healthy subjects. In contrast genes involved in cell adhesion molecules, cytokine-cytokine receptor interaction, insulin signaling and immune system pathways are downregulated in obese. Genes involved in signal transduction, regulation of actin cytoskeleton, antigen processing and presentation, complement and coagulation cascades, aXon guidance and neurodegenerative disorders pathways are upregulated in subjects with type 2 diabetes with family history of diabetes compared to those who are diabetic but with no family history. Genes involved in oXidative phosphorylation, immune, nervous system, and Metabolic disorders pathways are upregulated in those with diabetes with family history of diabetes compared to those with diabetes but with no family history. In contrast, genes involved in lipid and amino acid pathways, ubiquitin mediated proteolysis, signal transduction, insulin signaling and PPAR signaling pathways are downregulated in subjects with diabetes with family history of diabetes. It was noted that genes involved in inflammatory pathway are differentially eXpressed both in obesity and type 2 diabetes. These results suggest that genes concerned with carbohydrate, lipid and amino acid Metabolic pathways, neuronal function and inflammation play a significant role in the pathobiology of obesity and type 2 diabetes.
-
Is Metabolic Syndrome X a disorder of the brain with the initiation of low-grade systemic inflammatory events during the perinatal period?
The Journal of nutritional biochemistry, 2007Co-Authors: Undurti N. DasAbstract:Abstract An imbalance between pro- and anti-inflammatory molecules occurs in Metabolic Syndrome X. High-energy diet, saturated fats and trans -fats during perinatal period could suppress Δ 6 and Δ 5 desaturases both in the maternal and fetal tissues, resulting in a decrease in the concentrations of long-chain polyunsaturated fatty acids (LCPUFAs): arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosaheXaenoic acid (DHA) that have a negative feedback control on inflammation. EPA, DHA and AA augment endothelial nitric oXide synthesis, potentiate insulin action both in the peripheral tissues and brain and alter leptin production. LCPUFAs are essential for brain growth and development and synaptogenesis and modulate the action of several neurotransmitters and hypothalamic peptides. This suggests that Metabolic Syndrome X could be a disorder of the brain due to suboptimal LCPUFAs during perinatal period that triggers low-grade systemic inflammation, implying that perinatal strategies are needed to prevent its development.
-
Is erectile dysfunction a low-grade systemic inflammatory condition?
European heart journal, 2007Co-Authors: Undurti N. DasAbstract:Low-grade systemic inflammation is present in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidaemia, and Metabolic Syndrome X, which predispose to the development of coronary heart disease (CHD),1,2 conditions in which endothelial dysfunction is present, implying that reduced production of nitric oXide (NO) by endothelial cells could be a common denominator. NO, produced by endothelial cells, is responsible for penile erection. Hence, obesity, type 2 diabetes mellitus, hypertension, hyperlipidaemia, and Metabolic Syndrome X are likely to be associated with erectile dysfunction. The findings of Montorsi et al. 3 and Vlachopoulos et al. 4 are not only in support of this …
-
EXercise and inflammation.
European Heart Journal, 2006Co-Authors: Undurti N. DasAbstract:Low-grade systemic inflammation is present in subjects with insulin resistance, obesity, type-2 diabetes mellitus, hypertension, hyperlipidaemia, and Metabolic Syndrome X.1–3 The results of the study reported by Lakka et al .4 suggest that eXercise reduces the concentrations of pro-inflammatory molecule C-reactive protein. These results are in support of my earlier proposition that eXercise is anti-inflammatory in nature.5 Studies revealed that eXercise not only decreased the levels of pro-inflammatory cytokines IL-6, TNF-α, and C-reactive protein but also simultaneously enhanced the concentrations of …
-
Long-Chain Polyunsaturated Fatty Acids and Metabolic Syndrome X
Nutrients Stress and Medical Disorders, 2006Co-Authors: Undurti N. DasAbstract:Metabolic Syndrome X is characterized by abdominal obesity, atherosclerosis, insulin resistance and hyperinsulinemia, hyperlipidemias, essential hypertension, type 2 diabetes mellitus, and coronary heart disease (CHD). Other minor features of Metabolic Syndrome X include hyperfibrinogenemia, increased plasminogen activator inhibitor-1 (PAI-1), low tissue plasminogen activator, nephropathy, microalbuminuria, and hyperuricemia (Das, 2002a). The incidence of Metabolic Syndrome X is increasing throughout the world. The cause(s) for this increasing incidence is not clear. Because genetics of various populations have not changed in the last 100 yr, it is likely that environmental factors play a major role in the increasing incidence of Metabolic Syndrome X.
Rodney A. Velliquette - One of the best experts on this subject based on the ideXlab platform.
-
Lipid-lowering actions of imidazoline antihypertensive agents in Metabolic Syndrome X
Naunyn-Schmiedeberg's archives of pharmacology, 2006Co-Authors: Rodney A. Velliquette, Rachel Kossover, Stephen F. Previs, Paul ErnsbergerAbstract:Agonists active at I1-imidazoline receptors (I1R) not only lower blood pressure but also ameliorate glucose intolerance, insulin resistance, and hyperlipidemia with long-term treatment. We sought to determine the possible mechanism for the lipid-lowering actions of imidazolines in a model of Metabolic Syndrome X, the spontaneously-hypertensive obese (SHROB) rat. The acute actions of moXonidine and rilmenidine, selective I1R agonists, were compared to a specific alpha2-adrenergic receptor agonist, guanabenz, with and without selective receptor blockers. MoXonidine and rilmenidine rapidly reduced plasma triglyceride (20+/-4% and 21+/-5%, respectively) and cholesterol (29+/-9% and 27+/-9%). In contrast, the specific alpha2-adrenergic receptor agonist guanabenz failed to reduce plasma lipids. Blocking eXperiments showed that moXonidine's actions were mediated by I1R and not alpha2-adrenergic receptors. To evaluate a hepatic site of action, radioligand binding studies with liver plasma membranes confirmed the presence of I1R. Intraportal moXonidine reduced plasma triglycerides by 23+/-3% within 10 min. MoXonidine inhibited hepatic triglyceride secretion by 75% compared to vehicle treatment. Tracer studies with 2H2O suggested that moXonidine inhibits de novo fatty acid synthesis. Thus, activation of I1R lowers plasma lipids, with the main site of action probably within the liver to reduce synthesis and secretion of triglycerides. More selective I1R agonists might provide monotherapy for hyperlipidemic hypertension.
-
Therapeutic actions of an insulin receptor activator and a novel peroXisome proliferator-activated receptor γ agonist in the spontaneously hypertensive obese rat model of Metabolic Syndrome X
The Journal of pharmacology and experimental therapeutics, 2005Co-Authors: Rodney A. Velliquette, Jacob E. Friedman, Jianhua Shao, Bei B. Zhang, Paul ErnsbergerAbstract:Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as Metabolic Syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroXisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoXy-2-propylphenoXy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of Syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg X min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold eXcess fasting insulin and increased insulin AUC (6300 ng X min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with Metabolic Syndrome but via distinct mechanisms.
-
The Role of I1-Imidazoline Receptors and a2-Adrenergic Receptors in the Modulation of Glucose and Lipid Metabolism in the SHROB Model of Metabolic Syndrome X
Annals of the New York Academy of Sciences, 2003Co-Authors: Richard J. Koletsky, Rodney A. Velliquette, Paul ErnsbergerAbstract:Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as Metabolic Syndrome X. With the notable eXception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of Metabolic Syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moXonidine have miXed effects on components of Metabolic Syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of Metabolic Syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moXonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moXonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moXonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.
-
The Role of I1-Imidazoline and α2-Adrenergic Receptors in the Modulation of Glucose Metabolism in the Spontaneously Hypertensive Obese Rat Model of Metabolic Syndrome X
The Journal of pharmacology and experimental therapeutics, 2003Co-Authors: Rodney A. Velliquette, Paul ErnsbergerAbstract:We eXamined glucose metabolism after I 1 -imidazoline (I 1 R) and α 2 -adrenergic receptor (α 2 AR) activation in an animal model of Metabolic Syndrome X. Fasted spontaneously hypertensive obese rats (SHROB) were given the I 1 R/α 2 AR agonists moXonidine and rilmenidine or the α 2 AR agonist guanabenz. Because of the dual specificity of moXonidine, its actions were split into adrenergic and nonadrenergic components by using selective antagonists: rauwolscine (α 2 AR) efaroXan (I 1 R/α 2 AR), or 2-endo-amino-3-eXo-isopropylbicyclo[2.2.1.]heptane (AGN 192403) (I 1 R). Hyperglycemia induced by moXonidine, rilmenidine, and guanabenz resulted from inhibition of insulin secretion. Similar responses were observed after oral dosing and in lean littermates. Glucagon was reduced by the I 1 R agonists (moXonidine, 32 ± 5%; rilmenidine, 24 ± 7%) but elevated by guanabenz (71 ± 32%). The hyperglycemic and hypoinsulinemic responses to moXonidine were blocked by rauwolscine. In contrast, rauwolscine potentiated the reduction in glucagon (39 ± 6%). AGN 193402 blocked the glucagon response without affecting hyperglycemia and hypoinsulinemia. EfaroXan blocked all responses to moXonidine. When SHROB rats were treated with moXonidine 15 min before an oral glucose tolerance test, the glucose area under the curve (AUC) was increased. Antagonizing the α 2 AR component of moXonidine9s action with rauwolscine improved glucose AUC 3-fold and facilitated the insulin secretory response and reduced glucagon secretion. Testing fasting glucose and insulin during 3 weeks of oral moXonidine revealed early hyperglycemia that later faded, and a progressive drop in fasting insulin. The acute hyperglycemia and hypoinsulinemia elicited by moXonidine and rilmenidine was mediated by α 2 AR, whereas I 1 R may reduce glucagon and increase insulin, particularly after a glucose load.
-
Plasma glucagon and free fatty acid responses to a glucose load in the obese spontaneous hypertensive rat (SHROB) model of Metabolic Syndrome X.
Experimental biology and medicine (Maywood N.J.), 2002Co-Authors: Rodney A. Velliquette, Richard J. Koletsky, Paul ErnsbergerAbstract:Metabolic Syndrome X is a cluster of abnormalities including insulin resistance, hyperlipidemia, hypertension, and obesity. We sought to determine if eXcess plasma glucagon and free fatty acids (FFA) might contribute to the insulin resistance in the obese spontaneous hypertensive rat (SHROB), a unique animal model of leptin resistance and Metabolic Syndrome X. SHROB were eXtremely hyperinsulinemic and mildly glucose intolerant compared with lean SHR. SHROB had elevated fasting plasma glucagon and FFA, and showed paradoXical responses to an oral glucose challenge, with increased glucagon at 30 and 60 min postchallenge (200% ± 45% and 91% ± 13%, respectively; n = 9). In lean SHR, glucagon was nearly unchanged by glucose loading ( 0.05; n = 5). Plasma FFA were not affected by a glucose load in SHROB, whereas SHR showed a decrease of 40% ± 6% (n = 5–9). The I/G molar ratio changed in opposite directions in the two genotypes, with a decrease in SHROB at 30 and 60 min, in contrast to the appro...
Parameswara Achutha Kurup - One of the best experts on this subject based on the ideXlab platform.
-
Endosymbiotic Archaea and Hyperammonemic Syndrome
2019Co-Authors: Ravikumar Kurup, Parameswara Achutha KurupAbstract:Archaeal endosymbiosis leads to induction of the Warburg phenotype and increased glycolysis as well as mitochondrial dysfunction. The pyruvate generated consequent to the glycolytic cascade enters the GABA shunt where it is converted to glutamate, GABA and succinyl CoA. The pyruvate is converted to glutamate which gets acted upon by glutamate dehydrogenase generating ammonia. The endosymbiotic archaea can oXidize ammonia for its energetics. Archaeal cholesterol catabolism mediated by archaeal cholesterol oXidase can also produce cholesterol ring oXidation to generate pyruvate. Pyruvate is converted to glutamate by the enzyme serum glutamate pyruvate transaminase. The glutamate gets acted upon by glutamate dehydrogenase to generate ammonia. Archaeal urease can act upon urea generating ammonia and thiocyanate. The archaea are ammonia oXidizing and can use ammonia for their energetics. The archaeal urease activity related ammonia and thiocyanate synthesis as well as cholesterol oXidase activity generating pyruvate and ammonia are important schizophrenia, malignancy, Metabolic Syndrome X, autoimmune disease and neuronal degeneration.
-
Climate Change Mediated Actinidic Archaeal Endosymbiosis Generates Neanderthal Hybrids and Mind-Body Phenotypic Change
Advances in Natural Science, 2013Co-Authors: Ravikumar Kurup, Parameswara Achutha KurupAbstract:Actinidic archaea has been related to global warming and human diseases especially autoimmune disease, neuro-degeneration, neuropsychiatric disorder, neoplasm and Metabolic Syndrome X. The growth of endosymbiotic actinidic archaea in relation to climate change and global warming leads to nean-derthalisation of the human mind-body system. Neanderthal anthropometry and metabolonomics has been described in autoimmune disease, neuro-degeneration, neuropsychiatric disorder, neoplasm and Metabolic Syndrome X especially the Warburg phenotype and hyperdigoXinemia. DigoXin produced by archaeal cholesterol catabolism produces Nean-derthalisation. Prefrontal cortical atrophy and cerebellar hyperplasia has been related to autoimmune disease, neuro-degeneration, neuropsychiatric disorder, neoplasm and Metabolic Syndrome X in this communication. This leads on to dysautonomia with sympathetic hyperactivity and parasympathetic neuropathy in these disorders. Actinidic archaeal related cerebellar dominance leads to changes in brain function. The data is described in this paper.
-
porphyrins regulate the Metabolic and endocrine system role in generation of warburg phenotype endogenous digoXin synthesis and Metabolic Syndrome X with type 2 diabetes mellitus
Advances in Natural Science, 2012Co-Authors: Ravikumar A Kurup, Parameswara Achutha KurupAbstract:Objectives : Actinidic archaea have been related to the pathogenesis of Metabolic Syndrome X. An actinide dependent shadow biosphere of archaea and viroids has been described in Metabolic Syndrome X with type 2 diabetes mellitus. Actinidic archaea have a mevalonate pathway and are cholesterol catabolizing. They can use cholesterol as a carbon and energy source. Archaeal cholesterol catabolism can generate porphyrins via the cholesterol ring oXidase generated pyruvate and GABA shunt pathway. Archaea can produce a secondary porphyria by inducing the enzyme heme oXygenase resulting in heme depletion and activation of the enzyme ALA synthase. Porphyrins have been related to Metabolic Syndrome X and type 2 diabetes mellitus. The role of archaeal porphyrins in regulation of cell functions, metabolism and endocrine function is discussed. Porphyrins play a key role in the generation of the Warburg phenotype, endogenous digoXin synthesis and Metabolic Syndrome X with type 2 diabetes mellitus. Methodology : The following groups were included in the study: - Metabolic Syndrome X with cerebrovascular thrombosis and coronary artery disease. There were 10 patients in each group and each patient had an age and seX matched healthy control selected randomly from the general population. The blood samples were drawn in the fasting state before treatment was initiated. Plasma from fasting heparinised blood was used and the eXperimental protocol was as follows (I) Plasma + phosphate buffered saline, (II) same as I + cholesterol substrate, (III) same as II + rutile 0.1 mg/ml, (IV) same as II + ciprofloXacine and doXycycline each in a concentration of 1 mg/ml. The following estimations were carried out: - Cytochrome F420, free RNA, free DNA, polycyclic aromatic hydrocarbon, hydrogen peroXide, pyruvate, ammonia, glutamate, succinate, glycine, delta aminolevulinic acid and digoXin. The study also involved estimating the following parameters in the patient population- heXokinase, porphyrins, pyruvate, glutamate, ammonia, succinic acid, serine, glycine, HMG CoA reductase, cytochrome C, blood ATP and heme oXygenase. Results : Plasma of control subjects showed increased levels of the above mentioned parameters with after incubation for 1 hour and addition of cholesterol substrate resulted in still further significant increase in these parameters. The plasma of patients showed similar results but the eXtent of increase was more. The addition of antibiotics to the control plasma caused a decrease in all the parameters while addition of rutile increased their levels. The addition of antibiotics and rutile to the patient’s plasma produced the same changes but the eXtent of change was more in patient’s sera as compared to controls. There was upregulated archaeal porphyrin synthesis in the patient population which was archaeal in origin as indicated by actinide catalysis of the reactions. The cholesterol oXidase pathway generated pyruvate which entered the GABA shunt pathway. This resulted in synthesis of succinate and glycine which are substrates for ALA synthase. The study showed the patient’s blood had increased heme oXygenase activity, increased serine, glycine, succinic acid and porphyrins. The heXokinase activity was high. The pyruvate, glutamate, ammonia, GABA and succinic acid levels were elevated indicating blockade of PDH activity, and operation of the GABA shunt pathway. The cytoC levels were increased in the serum indicating mitochondrial dysfunction suggested by low blood ATP levels. This was indicative of the Warburg’s phenotype. The HMG CoA reductase activity was high indicating cholesterol synthesis. The RHCD population had values similar to the patient population. The LHCD population had opposite values. Conclusion: An actinide dependent shadow biosphere of archaea and viroids in Metabolic Syndrome X with coronary and cerebrovascular diseases. The porphyrins can contribute to the pathogenesis of Metabolic Syndrome X with coronary and cerebrovascular diseases. Porphyrin synthesis is crucial in the pathogenesis of these disorders. Porphyrins may serve as regulatory molecules modulating immune, neural, endocrine, Metabolic and genetic systems. The porphyrins photo-oXidation generated free radicals can produce immune activation, produce cell death, activate cell proliferation, produce insulin resistance and modulate conscious/quantal perception. Porphyrins can regulate hemispheric dominance. The archaeal porphyrins functions as key regulatory molecules with mitochondrial benzodiazepine receptors playing an important role. Key words : Actinide; Archaea; Porphyrins; GABA shunt; Peripheral benzodiazepine receptor; Delta aminolevulinic acid; Metabolic Syndrome X; Type 2 diabetes mellitus; Coronary artery disease; Cerebrovascular disease
-
The Lotus of Brahma- Volume II Porphyrins and Civilizational Disease
2012Co-Authors: Ravikumar Kurup, Parameswara Achutha KurupAbstract:An actinide dependent shadow biosphere of archaea and viroids and related disorder of porphyrin metabolism can contribute to the pathogenesis of Metabolic Syndrome X, malignancy, psychiatric disorders, autoimmune disease, AIDS, prion disease, neuronal degeneration and epileptogenesis. These are civilizational diseases. Archaeal porphyrin synthesis is crucial in the pathogenesis of these disorders. Porphyrins may serve as regulatory molecules modulating immune, neural, endocrine, Metabolic and genetic systems. The porphyrins photo-oXidation generated free radicals can produce immune activation, produce cell death, activate cell proliferation, produce insulin resistance and modulate conscious/ quantal perception. Porphyrins can regulate hemispheric dominance. The archaeal porphyrins functions as key regulatory molecules with mitochondrial benzodiazepine receptors playing an important role. The role of porphyrins in abiogenesis and origin of life as well as biological universe is discussed
-
Endosymbiotic Actinidic Archaeal DigoXin Inhibited Sodium Potassium ATPase Mediated ATP Synthesis and Archaeal Ectoatpases Produce Neuro-Immuno- Metabolic-Endocrine/Cell Cycle Regulation
Advances in Natural Science, 2012Co-Authors: A Ravikumar Kurup, Parameswara Achutha KurupAbstract:Aims and Objectives: Actinidic archaea has been related to the pathogenesis of schizophrenia, malignancy, Metabolic Syndrome X, autoimmune disease and neuronal degeneration. Archaea have got ecto ATPases. EctoATPases convert ATP to ADP and AMP. ATP functions as purinergic neurotransmitter regulating multiple cell functions. 5′AMP activates the Metabolic gauge AMP kinase. Archaeal digoXin produces membrane sodium potassium ATPase inhibition. Membrane sodium potassium ATPase in the setting of digoXin induced inhibition can synthesize ATP. This ATP can serve as a substrate for ectoATPase and functions as a archaeal signalling molecule. The RBC membrane sodium potassium ATPase mediated ATP synthesis and archaeal ectoATPase activity was assessed in the above mentioned disorders. Methodology: The following groups were included in the study:- endomyocardial fibrosis, alzheimer’s disease, multiple sclerosis, non-hodgkin’s lymphoma, Metabolic Syndrome X with cerebrovascular thrombosis and coronary artery disease, schizophrenia, autism, seizure disorder, creutzfeldt jakob disease and acquired immunodeficiency Syndrome. Plasma from fasting heparinised blood was used and the eXperimental protocol was as follows (I) Plasma+phosphate buffered saline, (II) same as I+cholesterol substrate, (III) same as II+rutile 0.1 mg/ml, (IV) same as II+ciprofloXacine and doXycycline each in a concentration of 1 mg/ml. The following three estimations were carried out:- Cytochrome F420 and ectoATPase activity. RBCs from the patient’s blood were separated within 1 hour of collection of blood and ATP synthesis activity was assessed in the presence of added digoXin to produce a concentration 12.2 ng/dl. Results: Plasma of control subjects showed increased levels of the above mentioned parameters with after incubation for 1 hour and addition of cholesterol substrate resulted in still further significant increase in these parameters. The plasma of patients showed similar results but the eXtent of increase was more. The addition of antibiotics to the control plasma caused a decrease in all the parameters while addition of rutile increased their levels. The addition of antibiotics and rutile to the patient’s plasma produced the same changes but the eXtent of change was more in patient’s sera as compared to controls. There was RBC membrane ATP synthesis in the patient population in the presence of added digoXin indicating membrane sodium potassium ATPase mediated ATP synthesis. Conclusion: An actinide dependent shadow biosphere of archaea in the above mentioned disease states is described. There was RBC membrane sodium potassium ATPase mediated ATP synthesis and serum archaeal ectoATPase activity in the patients with schizophrenia, malignancy, Metabolic Syndrome X, autoimmune disease and neuronal degeneration. The ectoATPase can degrade the RBC membrane synthesized ATP to 5’AMP which can activate AMPK producing Metabolic integration. The membrane sodium potassium ATPase synthesized ATP acts as a purinergic transmitter regulating immunity, neural function and cell differentitation/death. Key words: Actinide; Archaea; EXtracellular ATP; Sodium potassium ATPase; EctoATPases; AMPK; purinergic transmission
Brian R. Walker - One of the best experts on this subject based on the ideXlab platform.
-
Steroid metabolism in Metabolic Syndrome X.
Best Practice & Research Clinical Endocrinology & Metabolism, 2001Co-Authors: Brian R. WalkerAbstract:Abstract Preceding chapters in this volume describe relatively rare conditions associated with qualitative rather than quantitative changes in enzymes involved in steroid synthesis and metabolism. In this chapter, several eXamples show how more subtle variations in activities of the same enzymes may be important in the pathophysiology of common diseases of compleX aetiology. This chapter reviews evidence for deranged steroid metabolism in patients with the ‘insulin resistance Syndrome’. In summary, patients with essential hypertension may have subtle 11β-hydroXylase or 11β-hydroXysteroid dehydrogenase type 2 deficiency resulting in mild mineralocorticoid eXcess. Patients with obesity, and/or associated hirsutism or hyperglycaemia, have evidence of altered peripheral metabolism of androgens (increased 5α-reductase) and glucocorticoids (altered 11β-hydroXysteroid dehydrogenase type 1, resulting in enhanced cortisol levels in adipose tissue). Some of these changes in steroid metabolism lend themselves to therapeutic manipulation which may provide novel strategies to reduce cardiovascular risk.
-
Steroid metabolism in Metabolic Syndrome X.
Best practice & research. Clinical endocrinology & metabolism, 2001Co-Authors: Brian R. WalkerAbstract:Preceding chapters in this volume describe relatively rare conditions associated with qualitative rather than quantitative changes in enzymes involved in steroid synthesis and metabolism. In this chapter, several eXamples show how more subtle variations in activities of the same enzymes may be important in the pathophysiology of common diseases of compleX aetiology. This chapter reviews evidence for deranged steroid metabolism in patients with the 'insulin resistance Syndrome'. In summary, patients with essential hypertension may have subtle 11beta-hydroXylase or 11beta-hydroXysteroid dehydrogenase type 2 deficiency resulting in mild mineralocorticoid eXcess. Patients with obesity, and/or associated hirsutism or hyperglycaemia, have evidence of altered peripheral metabolism of androgens (increased 5alpha-reductase) and glucocorticoids (altered 11beta-hydroXysteroid dehydrogenase type 1, resulting in enhanced cortisol levels in adipose tissue). Some of these changes in steroid metabolism lend themselves to therapeutic manipulation which may provide novel strategies to reduce cardiovascular risk.