Due to its properties, paper represents an alternative to perform point-of-care tests for colorim... more Due to its properties, paper represents an alternative to perform point-of-care tests for colorimetric determination of glucose levels, providing simple, rapid, and inexpensive means of diagnosis. In this work, we report the development of a novel, rapid, disposable, inexpensive, enzyme-free, and colorimetric paper-based assay for glucose level determination. This sensing strategy is based on the synthesis of gold nanoparticles (AuNPs) by reduction of a gold salt precursor, in which glucose acts simultaneously as reducing and capping agent. This leads to a direct measurement of glucose without any enzymes or depending on the detection of intermediate products as in conventional enzymatic colorimetric methods. Firstly, we modelled the synthesis reaction of AuNPs to determine the optical, morphological, and kinetic properties and their manipulation for glucose sensing, by determining the influence of each of the reaction precursors towards the produced AuNPs, providing a guide for the...
The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase... more The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete. The current study was designed to test the hypothesis that treatment with S-nitrosoglutathione is sufficient to revert insulin resistance induced by a high-sucrose diet. Male Wistar rats were divided in a control or high-sucrose group. Insulin sensitivity was determined: (i) in the fast state; (ii) after a standardized test meal; (iii) after GSH + NO; and after (iv) S-nitrosoglutathione (GSNO) administration. The fasting glucose level was not different between the control and high-sucrose group. In the liver, the high-sucrose model shows increased NO and unchanged GSH levels. In control animals, ...
Aims Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. ... more Aims Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores – for example, the Dutch Lipid Score – are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a “virtual” genetic test using machine-learning approaches. Methods and results We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data ( N = 174) and internal test ( N = 74)) and the FH-CEGP Milan cohort (external test, N = 364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machi...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepat... more Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone...
The neuroprotective role of natural polyphenols is well established but phenolics poor water solu... more The neuroprotective role of natural polyphenols is well established but phenolics poor water solubility affects their bioavailability and bioactivity. Aiming to overcome this issue, we were encouraged to investigate the 2-deoxyglycosylation of natural or nature inspired neuroprotective molecules, using glycals as easily accessed glycosyl donors. This robust methodology allowed the generation of a set of new resveratrol and caffeic acid ester glycosides, envisioning more effective and bioavailable compounds. Resveratrol 2-deoxyglycosides were more effective at protecting the neuronal cells from peroxide-induced cytotoxicity than resveratrol itself, while the caffeic acid ester glycoside also showed extraordinary neuroprotection activity. Coefficient partition measurements demonstrated the moderate lipophilicity of resveratrol glycosides, which Log D values are typical of a central nervous system (CNS) drug and ideal for blood-brain barrier (BBB) penetration. Passive permeation assess...
With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the... more With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones...
A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo ... more A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo (H. Xie, L. Zhu, Y.L. Zhang, D.J. Legare, and W.W. Lautt. J. Pharmacol. Toxicol. Methods, 35: 77-82. 1996). This technical report describes the current recommended standard operating procedure for the use of the RIST in rats based upon additional experience with approximately 100 tests. We describe the manufacture and use of an arterial-venous shunt that allows rapid multiple arterial samples and intravenous administration of drugs. The RIST procedure involves determination of a stable arterial glucose baseline to define the ideal euglycemic level to be maintained following a 5-min infusion of insulin, with the RIST index being the amount of glucose required to be infused to maintain euglycemia over the test period. Insulin administration by a 5-min infusion is preferable to a 30-s bolus administration. No significant difference was determined between the use of Toronto pork-beef or human insulin. Four consecutive RISTs were carried out in the same animal over 4-5 h with no tendency for change with time. The RIST index is sufficiently sensitive and reproducible to permit establishment of insulin dose-response curves and interference of insulin action by elimination of hepatic parasympathetic nerves, using atropine. This technical report provides the current recommended standard operating procedure for the RIST.Key words: insulin, resistance, test, methodology, glucose.
Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activ... more Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0%; LZR, 40.1 +/- 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6%; LZR, 46.4 +/- 4.1%), similar to that after atropine. We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.
A liquid chromatography tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring (M... more A liquid chromatography tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring (MRM) in a triple-quadrupole scan mode was developed and comprehensively validated for the determination of [6,6-(2)H2]glucose and [U-(13)C6]glucose enrichments from dried blood spots (DBS) without prior derivatization. The method is demonstrated with dried blood spots obtained from rats administered with a primed-constant infusion of [U-(13)C6]glucose and an oral glucose load enriched with [6,6-(2)H2]glucose. The sensitivity is sufficient for analysis of the equivalent to <5μL of blood and the overall method was accurate and precise for the determination of DBS isotopic enrichments.
Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growi... more Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary-adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication.
Thiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the und... more Thiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the underlying mechanisms of their hepatic actions remain unclear. Hepatic triglyceride content and export rates were assessed in 2-week high-sucrose-fed Wistar rats treated with troglitazone (HS-T) and compared with untreated HS rodent controls (HS-C). Fractional de novo lipogenesis contributions to hepatic triglyceride were quantified by analysis of triglyceride enrichment from deuterated water. Hepatic insulin clearance and nitric oxide (NO) status during a meal tolerance test were also evaluated. TZD significantly reduced hepatic triglyceride (p < 0.01) by 48%, decreased de novo lipogenesis contribution to hepatic triglyceride (p < 0.01) and increased postprandial non-esterified fatty acids (NEFA) clearance rates (p < 0.01) in comparison to HS-C group. During a meal tolerance test, plasma insulin area-under-the curve was significantly lower (p < 0.01) while blood glucose and plasma C-peptide levels were not different. Insulin clearance was increased…
Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepat... more Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone...
Due to its properties, paper represents an alternative to perform point-of-care tests for colorim... more Due to its properties, paper represents an alternative to perform point-of-care tests for colorimetric determination of glucose levels, providing simple, rapid, and inexpensive means of diagnosis. In this work, we report the development of a novel, rapid, disposable, inexpensive, enzyme-free, and colorimetric paper-based assay for glucose level determination. This sensing strategy is based on the synthesis of gold nanoparticles (AuNPs) by reduction of a gold salt precursor, in which glucose acts simultaneously as reducing and capping agent. This leads to a direct measurement of glucose without any enzymes or depending on the detection of intermediate products as in conventional enzymatic colorimetric methods. Firstly, we modelled the synthesis reaction of AuNPs to determine the optical, morphological, and kinetic properties and their manipulation for glucose sensing, by determining the influence of each of the reaction precursors towards the produced AuNPs, providing a guide for the...
The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase... more The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete. The current study was designed to test the hypothesis that treatment with S-nitrosoglutathione is sufficient to revert insulin resistance induced by a high-sucrose diet. Male Wistar rats were divided in a control or high-sucrose group. Insulin sensitivity was determined: (i) in the fast state; (ii) after a standardized test meal; (iii) after GSH + NO; and after (iv) S-nitrosoglutathione (GSNO) administration. The fasting glucose level was not different between the control and high-sucrose group. In the liver, the high-sucrose model shows increased NO and unchanged GSH levels. In control animals, ...
Aims Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. ... more Aims Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism. The gold standard for FH diagnosis is genetic testing, available, however, only in selected university hospitals. Clinical scores – for example, the Dutch Lipid Score – are often employed as alternative, more accessible, albeit less accurate FH diagnostic tools. The aim of this study is to obtain a more reliable approach to FH diagnosis by a “virtual” genetic test using machine-learning approaches. Methods and results We used three machine-learning algorithms (a classification tree (CT), a gradient boosting machine (GBM), a neural network (NN)) to predict the presence of FH-causative genetic mutations in two independent FH cohorts: the FH Gothenburg cohort (split into training data ( N = 174) and internal test ( N = 74)) and the FH-CEGP Milan cohort (external test, N = 364). By evaluating their area under the receiver operating characteristic (AUROC) curves, we found that the three machi...
American Journal of Physiology-Gastrointestinal and Liver Physiology
Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepat... more Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone...
The neuroprotective role of natural polyphenols is well established but phenolics poor water solu... more The neuroprotective role of natural polyphenols is well established but phenolics poor water solubility affects their bioavailability and bioactivity. Aiming to overcome this issue, we were encouraged to investigate the 2-deoxyglycosylation of natural or nature inspired neuroprotective molecules, using glycals as easily accessed glycosyl donors. This robust methodology allowed the generation of a set of new resveratrol and caffeic acid ester glycosides, envisioning more effective and bioavailable compounds. Resveratrol 2-deoxyglycosides were more effective at protecting the neuronal cells from peroxide-induced cytotoxicity than resveratrol itself, while the caffeic acid ester glycoside also showed extraordinary neuroprotection activity. Coefficient partition measurements demonstrated the moderate lipophilicity of resveratrol glycosides, which Log D values are typical of a central nervous system (CNS) drug and ideal for blood-brain barrier (BBB) penetration. Passive permeation assess...
With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the... more With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones...
A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo ... more A rapid insulin sensitivity test (RIST) was recently introduced to assess insulin action in vivo (H. Xie, L. Zhu, Y.L. Zhang, D.J. Legare, and W.W. Lautt. J. Pharmacol. Toxicol. Methods, 35: 77-82. 1996). This technical report describes the current recommended standard operating procedure for the use of the RIST in rats based upon additional experience with approximately 100 tests. We describe the manufacture and use of an arterial-venous shunt that allows rapid multiple arterial samples and intravenous administration of drugs. The RIST procedure involves determination of a stable arterial glucose baseline to define the ideal euglycemic level to be maintained following a 5-min infusion of insulin, with the RIST index being the amount of glucose required to be infused to maintain euglycemia over the test period. Insulin administration by a 5-min infusion is preferable to a 30-s bolus administration. No significant difference was determined between the use of Toronto pork-beef or human insulin. Four consecutive RISTs were carried out in the same animal over 4-5 h with no tendency for change with time. The RIST index is sufficiently sensitive and reproducible to permit establishment of insulin dose-response curves and interference of insulin action by elimination of hepatic parasympathetic nerves, using atropine. This technical report provides the current recommended standard operating procedure for the RIST.Key words: insulin, resistance, test, methodology, glucose.
Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activ... more Whole-body insulin sensitivity (IS) depends on a hepatic pathway, involving parasympathetic activation and hepatic nitric oxide (NO) production. Both atropine and N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor) induce insulin resistance (IR). IR is associated with obesity. Because NO action was shown to be impaired in animal models of obesity, such as the obese Zucker rat (OZR), we tested the hypothesis that the hepatic-dependent pathway is diminished in OZR, resulting in IR. Lean Zucker rats (LZRs) were used as OZR controls. IS was evaluated in terms of glucose disposal [milligrams of glucose per kilogram of body weight (bw)]. Two groups were submitted to two protocols. First, a control clamp was followed by a post-atropine (3 mg/kg intravenously) clamp. Second, after the control clamp, L-NMMA (0.73 mg/kg intraportally) was given, and a second clamp was performed. Hepatic-dependent IS was assessed by subtracting the response after atropine or L-NMMA from the basal response. In the first protocol, basal IS was lower in OZR than in LZR (OZR, 73.7 +/- 14.2; LZR, 289.2 +/- 24.7 mg glucose/kg bw; p < 0.001), and atropine decreased IS in the same proportion for both groups (OZR, 41.3 +/- 8.0%; LZR, 40.1 +/- 6.5%). Equally, in the second protocol, OZR presented lower IS (OZR, 79.3 +/- 1.6; LZR, 287.4 +/- 22.7 mg glucose/kg bw; p < 0.001). L-NMMA induced IS inhibition in both groups (OZR, 48.3 +/- 6.6%; LZR, 46.4 +/- 4.1%), similar to that after atropine. We show that the IR in OZR is due to similar impairment of both hepatic-dependent and -independent components of insulin action, suggesting the existence of a defect common to both pathways.
A liquid chromatography tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring (M... more A liquid chromatography tandem mass spectrometry (LC-MS/MS) using multiple reaction monitoring (MRM) in a triple-quadrupole scan mode was developed and comprehensively validated for the determination of [6,6-(2)H2]glucose and [U-(13)C6]glucose enrichments from dried blood spots (DBS) without prior derivatization. The method is demonstrated with dried blood spots obtained from rats administered with a primed-constant infusion of [U-(13)C6]glucose and an oral glucose load enriched with [6,6-(2)H2]glucose. The sensitivity is sufficient for analysis of the equivalent to <5μL of blood and the overall method was accurate and precise for the determination of DBS isotopic enrichments.
Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growi... more Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary-adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication.
Thiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the und... more Thiazolidinediones (TZD) are known to ameliorate fatty liver in type 2 diabetes. To date, the underlying mechanisms of their hepatic actions remain unclear. Hepatic triglyceride content and export rates were assessed in 2-week high-sucrose-fed Wistar rats treated with troglitazone (HS-T) and compared with untreated HS rodent controls (HS-C). Fractional de novo lipogenesis contributions to hepatic triglyceride were quantified by analysis of triglyceride enrichment from deuterated water. Hepatic insulin clearance and nitric oxide (NO) status during a meal tolerance test were also evaluated. TZD significantly reduced hepatic triglyceride (p < 0.01) by 48%, decreased de novo lipogenesis contribution to hepatic triglyceride (p < 0.01) and increased postprandial non-esterified fatty acids (NEFA) clearance rates (p < 0.01) in comparison to HS-C group. During a meal tolerance test, plasma insulin area-under-the curve was significantly lower (p < 0.01) while blood glucose and plasma C-peptide levels were not different. Insulin clearance was increased…
Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepat... more Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone...
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