Nieves Gonzalez - Academia.edu (original) (raw)
Papers by Nieves Gonzalez
Psychiatry Research, 2010
Our objective was to study gender differences in delusional disorder (DD), by comparing potential... more Our objective was to study gender differences in delusional disorder (DD), by comparing potential risk factors, clinical correlates, illness course characteristics, and functionality. The sample was composed of 86 outpatients with DD (according to the SCID-I for DSM-IV criteria). The following assessment instruments were used service use and demographic questionnaires, Standardized Assessment of Personality (SAP), the Positive and Negative Symptom Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Mini-Mental State Examination (MMSE), Mini International Neuropsychiatry Interview (MINI), Sheehan Disability Inventory (SDI), and the Global Assessment of Functioning (GAF) scale. The female-to-male ratio was 1.6:1. Men were more likely to be single, while women were more likely to be widows. Men had a greater frequency of schizoid and schizotypal premorbid personality disorders and of premorbid substance abuse. There were no differences for other risk factors (immigration, deafness, late onset, other personality disorders, and family history). Men were younger at onset and more frequently had acute onset of the disorder. Men had more severe symptoms (higher score on the global or separate PANSS scales). There were no gender differences for the remaining symptomatological variables (types of DD, presence and severity of depression, presence of hallucinations, severity of global cognitive functioning and presence of axis I comorbidity). Global and partial (work, family, and social) functioning was significantly poorer among men. Course type and consumption of resources appeared to be similar. We conclude that men with DD had significantly more severe symptoms and worse functionality. They also had a higher frequency of schizoid and schizotypal premorbid personality disorders and premorbid substance abuse.
PLoS ONE, 2013
Objective: Delusional disorder has been traditionally considered a psychotic syndrome that does n... more Objective: Delusional disorder has been traditionally considered a psychotic syndrome that does not evolve to cognitive deterioration. However, to date, very little empirical research has been done to explore cognitive executive components and memory processes in Delusional Disorder patients. This study will investigate whether patients with delusional disorder are intact in both executive function components (such as flexibility, impulsivity and updating components) and memory processes (such as immediate, short term and long term recall, learning and recognition).
European Psychiatry, 2008
A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe socio... more A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe sociodemographic and clinical correlates of DD and to identify clinical profiles associated to DD and its subtypes.This is a case-register study based on all those subjects attending community mental health services within a geographically well-defined area. Four hundred and sixty-seven patients had been diagnosed as DD cases at psychiatric services serving a catchment area of some 607,494 inhabitants living in South Barcelona (Spain) during a three-year period (2001–2003). A thorough systematic review of computerised medical records was used to establish DSM-IV diagnosis, rendering a valid sample of 370 patients who fulfilled DSM-IV criteria for DD. Independent variables gathered include sociodemographic data, family and personal psychiatric history, and comorbid diagnoses on all DSM-IV axes (including GAF). We used descriptive and univariate statistical methods to explore sample frequencies and correlates across DD types.The mean age of the patients was 55 years and the sample had a mean GAF score of 51 suggesting a poor functionality; 56.5% of the patients were female. The most frequent DD types were persecutory (48%), jealous (11%), mixed (11%) and somatic (5%), whilst 23% qualified for the NOS type. Most frequent symptoms identified were self-reference (40%), irritability (30%), depressive mood (20%) and aggressiveness (15%). Hallucinations were present in 16% of the patients (6% tactile; 4% olfactory). Nearly 9% had a family history of schizophrenia (higher among those with the jealous subtype) and 42% had a comorbid axis II diagnosis (mostly paranoid personality disorder). Depression was significantly more frequent among the persecutory and jealous types. Finally, global functioning was significantly better among jealous and mixed types and worse amongst erotomanic and grandiose cases (p = 0.008).In the absence of other similar empirical data, this modest study provides unique empirical evidence of some clinical and risk correlates of DD and its subtypes.
European Psychiatry, 2008
Objective. e A few empirically based studies' data on delusional disorder (DD) exist. We aim to d... more Objective. e A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe sociodemographic and clinical correlates of DD and to identify clinical profiles associated to DD and its subtypes.
Anthrozoos: A Multidisciplinary Journal of The Interactions of People & Animals, 2009
Address for correspondence: Victòria Villalta-Gil, Fundació Sant Joan de Déu, C/Sta. Rosa 3957, ... more Address for correspondence: Victòria Villalta-Gil, Fundació Sant Joan de Déu, C/Sta. Rosa 3957, 08950, Esplugues de Llobregat, Spain. E-mail: vvillalta@sjd-ssm.com The Schi-Can group is a multidisciplinary group of researchers, clinicians, and handlers that includes: ...
Regulatory Peptides, 2005
Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participat... more Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participating in glucose homeostasis, through receptors not associated to cAMP. In rat hepatocytes, activation of PI3K/PKB, PKC and PP-1 mediates the GLP-1-induced stimulation of glycogen synthase. We have investigated the effect of GLP-1 in normal human myocytes, and that of its structurally related peptides exendin-4 (Ex-4) and its truncated form 9-39 (Ex-9) upon glucose uptake, and the participation of cellular enzymes proposed to mediate insulin actions. GLP-1 and both exendins activated, like insulin, PI3K/PKB and p42/44 MAPK enzymes, but p70s6k was activated only by GLP-1 and insulin. GLP-1, Ex-4 and Ex-9, like insulin, stimulated glucose uptake; wortmannin blocked the action of GLP-1, insulin and Ex-9, and reduced that of Ex-4; PD98059 abolished the effect of all peptides/hormones, while rapamycin blocked that of insulin and partially prevented that of GLP-1. H-7 abolished the action of GLP-1, insulin and Ex-4, while Ro 31-8220 prevented only the Ex-4 and Ex-9 effect. In conclusion, GLP-1, like insulin, stimulates glucose uptake, and this involves activation of PI3K/PKB, p44/42 MAPKs, partially p70s6k, and possibly PKC; Ex-4 and Ex-9 both have GLP-1-like effect upon glucose transport, in which both share with GLP-1 an activation of PI3K/PKB —partially in the case of Ex-4— and p44/42 MAPKs but not p70s6k.
Peptides, 2009
The mammalian Bombesin (Bn) peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) actio... more The mammalian Bombesin (Bn) peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) actions are mediated by two receptors (NMB-receptor, GRP-receptor) which are widely distributed in the GI tract and CNS. From primarily animal studies NMB/GRP-receptor activation has physiological/pathophysiological effects in the CNS and GI tract including stimulating of growth of cancers and normal tissues. Whereas these Bn receptor's effects have been extensively studied in nonhuman cells and animals, little is known of the physiological/pathological role(s) in humans, largely due of lack of potent antagonists. To address this issue we compared NMB-receptor/GRPreceptor affinity/potency of 10 chemical classes of putative antagonists (35 compounds) for human Bn-receptors by performing binding studies or assessing abilities to activate hGRP/hNMB-receptor [assessing phospholipase C activation] in 4 different cells containing native Bn receptors or transfected receptors. From binding studies 23 were GRP-receptor-preferring, 4 were NMB-receptor, and 8-nonselective. For the hGRP-receptor-preferring analogues none showed hGRP-receptor agonist activity, but 13 were full or-partial hNMB-receptor agonists at hNMB-receptors. For hNMBreceptor-preferring analogues none were agonists. Analogue #24([(3-Ph-Pr 6 ),His 7 ,D-Ala 11 ,D-Pro 13 ,Ψ(13-14), Phe 14 ]Bn(6-14)NH 2 ) and analogue #7[D-Phe 6 ,Leu 13 ,Ψ(CH 2 NH),Cpa 14 ]Bn(6-14) were the most potent (0.2-1.4 nM) and selective ((>10, 000-fold) for the hGRP-receptor with analogue #7.5[D-Tpi 6 ,Leu 13 , Ψ(CH 2 NH),Leu 14 ]Bn(6-14) [RC-3095] (0.2-1.4 nM) slightly less selective. Analogue #34(PD168368) had the highest affinity for hNMB-receptor (1.32-1.58 nM) and the greatest selectivity (2298-6952-fold) for the hNMB-receptor. These results demonstrate numerous putative hGRP/hNMB-receptor antagonists identified in nonhuman cells and/or animals have agonist activity at the hNMB-receptor, limiting their potential usefulness. However, a number were identified which were potent/selective for human Bn receptors and should be useful for investigating their roles in human physiological/pathophysiological conditions.
Gastroenterology, 2010
Gastroenterology, Volume 138, Issue 5, Pages S-257, May 2010, Authors:Hirotsugu Uehara;Nieves Gon... more Gastroenterology, Volume 138, Issue 5, Pages S-257, May 2010, Authors:Hirotsugu Uehara;Nieves Gonzalez; Samuel A. Mantey; Tomoo Nakagawa; Tatsuro Katsuno; Robert T. Jensen. ...
Gastroenterology, 2008
Gastroenterology, Volume 134, Issue 4, Pages A-709, April 2008, Authors:Nieves Gonzalez; Samuel A... more Gastroenterology, Volume 134, Issue 4, Pages A-709, April 2008, Authors:Nieves Gonzalez; Samuel A. Mantey; Tapas K. Pradhan; Veronica Sancho; Terry W. Moody; David H. Coy; Robert T. Jensen.
Gastroenterology, 2009
BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share ... more BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share 50% homology, are both widely distributed in the GI tract/CNS, but their affinities for their natural occurring agonists [NMB ,GRP]markedly differ. Whereas, the basis of GRP's selectivity for GRPR is well-studied, little is known for NMBR. Previous studies suggested NMBR selectivity for NMB depends primarily on differences in the 3rd extracellular region (EC3) of the two receptors, particularly the presence of alanine (A) instead of isoleucine (I) (position 198,GRPR), histidine (H) instead of glutamine (G)(position 202, GRPR) and a serine (S)(position 215,GRPR) for isoleucine in transmembrane region 5 (TM5). However, the effect of these changes in combination or the molecular basis for the difference of affinity caused by these changes is unknown. AIM: To provide insight into effect of those important amino acids in combination and the molecular basis for differences in EC3/adjacent TM5 affecting NMB affinity for NMBR. METHODS: 3 double mutants (loss or gain of NMB affinity) were made in NMBR or GRPR combining amino acid differences in the EC3/TM5 that alone showed effects. 7 EC3 mutants in [H202]GRPR or 5 [I199]NMBR were made, where H202 or I199 were substituted by single amino acids with different chemical properties. Receptors were transiently expressed in Balb-3T3 cells and affinities determined. RESULTS: The [A198I,H202Q]mutation in GRPR increased 5-fold affinity which, was equal to the substitution of the entire EC3 NMBR domain, and greater than each point mutant alone.
Gastroenterology, 2009
BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share ... more BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share 50% homology, are both widely distributed in the GI tract/CNS, but their affinities for their natural occurring agonists [NMB ,GRP]markedly differ. Whereas, the basis of GRP's selectivity for GRPR is well-studied, little is known for NMBR. Previous studies suggested NMBR selectivity for NMB depends primarily on differences in the 3rd extracellular region (EC3) of the two receptors, particularly the presence of alanine (A) instead of isoleucine (I) (position 198,GRPR), histidine (H) instead of glutamine (G)(position 202, GRPR) and a serine (S)(position 215,GRPR) for isoleucine in transmembrane region 5 (TM5). However, the effect of these changes in combination or the molecular basis for the difference of affinity caused by these changes is unknown. AIM: To provide insight into effect of those important amino acids in combination and the molecular basis for differences in EC3/adjacent TM5 affecting NMB affinity for NMBR. METHODS: 3 double mutants (loss or gain of NMB affinity) were made in NMBR or GRPR combining amino acid differences in the EC3/TM5 that alone showed effects. 7 EC3 mutants in [H202]GRPR or 5 [I199]NMBR were made, where H202 or I199 were substituted by single amino acids with different chemical properties. Receptors were transiently expressed in Balb-3T3 cells and affinities determined. RESULTS: The [A198I,H202Q]mutation in GRPR increased 5-fold affinity which, was equal to the substitution of the entire EC3 NMBR domain, and greater than each point mutant alone.
Gastroenterology, 2008
the fusion fluorescent protein pRFP-LC3 was used as marker. We found that over expression of S100... more the fusion fluorescent protein pRFP-LC3 was used as marker. We found that over expression of S100A10 reduced significantly the recruitment of LC3 induced by VMP1 over expression. In conclusion we were able to find out a group of genes that potentially interact with VMP1 In Vivo and we demonstrated that the interaction VMP1-S100A10 reduces the formation of autophagosomes.
Journal of Molecular Endocrinology, 2005
Several kinases have been implicated in the metabolic response of human and rat myocytes to gluca... more Several kinases have been implicated in the metabolic response of human and rat myocytes to glucagon-like peptide-1 (GLP-1), exendin-4 (Ex-4) and exendin-9 (Ex-9). We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-D-glucose uptake, lipolysis and lipogenesis. The study was conducted in normal rats, and extended to a streptozotocin-induced type-2 diabetic model (STZ-rats). The participation of distinct kinases was estimated by using potential kinase inhibitors, including wortmannin, PD98059, rapamycin, H-7 and RO31-8220. In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. V SANCHO and others · Effects of GLP-1 and exendins on adipocytes of normal and diabetic rats
Psychiatry Research, 2010
Our objective was to study gender differences in delusional disorder (DD), by comparing potential... more Our objective was to study gender differences in delusional disorder (DD), by comparing potential risk factors, clinical correlates, illness course characteristics, and functionality. The sample was composed of 86 outpatients with DD (according to the SCID-I for DSM-IV criteria). The following assessment instruments were used service use and demographic questionnaires, Standardized Assessment of Personality (SAP), the Positive and Negative Symptom Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Mini-Mental State Examination (MMSE), Mini International Neuropsychiatry Interview (MINI), Sheehan Disability Inventory (SDI), and the Global Assessment of Functioning (GAF) scale. The female-to-male ratio was 1.6:1. Men were more likely to be single, while women were more likely to be widows. Men had a greater frequency of schizoid and schizotypal premorbid personality disorders and of premorbid substance abuse. There were no differences for other risk factors (immigration, deafness, late onset, other personality disorders, and family history). Men were younger at onset and more frequently had acute onset of the disorder. Men had more severe symptoms (higher score on the global or separate PANSS scales). There were no gender differences for the remaining symptomatological variables (types of DD, presence and severity of depression, presence of hallucinations, severity of global cognitive functioning and presence of axis I comorbidity). Global and partial (work, family, and social) functioning was significantly poorer among men. Course type and consumption of resources appeared to be similar. We conclude that men with DD had significantly more severe symptoms and worse functionality. They also had a higher frequency of schizoid and schizotypal premorbid personality disorders and premorbid substance abuse.
PLoS ONE, 2013
Objective: Delusional disorder has been traditionally considered a psychotic syndrome that does n... more Objective: Delusional disorder has been traditionally considered a psychotic syndrome that does not evolve to cognitive deterioration. However, to date, very little empirical research has been done to explore cognitive executive components and memory processes in Delusional Disorder patients. This study will investigate whether patients with delusional disorder are intact in both executive function components (such as flexibility, impulsivity and updating components) and memory processes (such as immediate, short term and long term recall, learning and recognition).
European Psychiatry, 2008
A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe socio... more A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe sociodemographic and clinical correlates of DD and to identify clinical profiles associated to DD and its subtypes.This is a case-register study based on all those subjects attending community mental health services within a geographically well-defined area. Four hundred and sixty-seven patients had been diagnosed as DD cases at psychiatric services serving a catchment area of some 607,494 inhabitants living in South Barcelona (Spain) during a three-year period (2001–2003). A thorough systematic review of computerised medical records was used to establish DSM-IV diagnosis, rendering a valid sample of 370 patients who fulfilled DSM-IV criteria for DD. Independent variables gathered include sociodemographic data, family and personal psychiatric history, and comorbid diagnoses on all DSM-IV axes (including GAF). We used descriptive and univariate statistical methods to explore sample frequencies and correlates across DD types.The mean age of the patients was 55 years and the sample had a mean GAF score of 51 suggesting a poor functionality; 56.5% of the patients were female. The most frequent DD types were persecutory (48%), jealous (11%), mixed (11%) and somatic (5%), whilst 23% qualified for the NOS type. Most frequent symptoms identified were self-reference (40%), irritability (30%), depressive mood (20%) and aggressiveness (15%). Hallucinations were present in 16% of the patients (6% tactile; 4% olfactory). Nearly 9% had a family history of schizophrenia (higher among those with the jealous subtype) and 42% had a comorbid axis II diagnosis (mostly paranoid personality disorder). Depression was significantly more frequent among the persecutory and jealous types. Finally, global functioning was significantly better among jealous and mixed types and worse amongst erotomanic and grandiose cases (p = 0.008).In the absence of other similar empirical data, this modest study provides unique empirical evidence of some clinical and risk correlates of DD and its subtypes.
European Psychiatry, 2008
Objective. e A few empirically based studies' data on delusional disorder (DD) exist. We aim to d... more Objective. e A few empirically based studies' data on delusional disorder (DD) exist. We aim to describe sociodemographic and clinical correlates of DD and to identify clinical profiles associated to DD and its subtypes.
Anthrozoos: A Multidisciplinary Journal of The Interactions of People & Animals, 2009
Address for correspondence: Victòria Villalta-Gil, Fundació Sant Joan de Déu, C/Sta. Rosa 3957, ... more Address for correspondence: Victòria Villalta-Gil, Fundació Sant Joan de Déu, C/Sta. Rosa 3957, 08950, Esplugues de Llobregat, Spain. E-mail: vvillalta@sjd-ssm.com The Schi-Can group is a multidisciplinary group of researchers, clinicians, and handlers that includes: ...
Regulatory Peptides, 2005
Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participat... more Glucagon-like peptide-1 (GLP-1) controls glucose metabolism in extrapancreatic tissues participating in glucose homeostasis, through receptors not associated to cAMP. In rat hepatocytes, activation of PI3K/PKB, PKC and PP-1 mediates the GLP-1-induced stimulation of glycogen synthase. We have investigated the effect of GLP-1 in normal human myocytes, and that of its structurally related peptides exendin-4 (Ex-4) and its truncated form 9-39 (Ex-9) upon glucose uptake, and the participation of cellular enzymes proposed to mediate insulin actions. GLP-1 and both exendins activated, like insulin, PI3K/PKB and p42/44 MAPK enzymes, but p70s6k was activated only by GLP-1 and insulin. GLP-1, Ex-4 and Ex-9, like insulin, stimulated glucose uptake; wortmannin blocked the action of GLP-1, insulin and Ex-9, and reduced that of Ex-4; PD98059 abolished the effect of all peptides/hormones, while rapamycin blocked that of insulin and partially prevented that of GLP-1. H-7 abolished the action of GLP-1, insulin and Ex-4, while Ro 31-8220 prevented only the Ex-4 and Ex-9 effect. In conclusion, GLP-1, like insulin, stimulates glucose uptake, and this involves activation of PI3K/PKB, p44/42 MAPKs, partially p70s6k, and possibly PKC; Ex-4 and Ex-9 both have GLP-1-like effect upon glucose transport, in which both share with GLP-1 an activation of PI3K/PKB —partially in the case of Ex-4— and p44/42 MAPKs but not p70s6k.
Peptides, 2009
The mammalian Bombesin (Bn) peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) actio... more The mammalian Bombesin (Bn) peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) actions are mediated by two receptors (NMB-receptor, GRP-receptor) which are widely distributed in the GI tract and CNS. From primarily animal studies NMB/GRP-receptor activation has physiological/pathophysiological effects in the CNS and GI tract including stimulating of growth of cancers and normal tissues. Whereas these Bn receptor's effects have been extensively studied in nonhuman cells and animals, little is known of the physiological/pathological role(s) in humans, largely due of lack of potent antagonists. To address this issue we compared NMB-receptor/GRPreceptor affinity/potency of 10 chemical classes of putative antagonists (35 compounds) for human Bn-receptors by performing binding studies or assessing abilities to activate hGRP/hNMB-receptor [assessing phospholipase C activation] in 4 different cells containing native Bn receptors or transfected receptors. From binding studies 23 were GRP-receptor-preferring, 4 were NMB-receptor, and 8-nonselective. For the hGRP-receptor-preferring analogues none showed hGRP-receptor agonist activity, but 13 were full or-partial hNMB-receptor agonists at hNMB-receptors. For hNMBreceptor-preferring analogues none were agonists. Analogue #24([(3-Ph-Pr 6 ),His 7 ,D-Ala 11 ,D-Pro 13 ,Ψ(13-14), Phe 14 ]Bn(6-14)NH 2 ) and analogue #7[D-Phe 6 ,Leu 13 ,Ψ(CH 2 NH),Cpa 14 ]Bn(6-14) were the most potent (0.2-1.4 nM) and selective ((>10, 000-fold) for the hGRP-receptor with analogue #7.5[D-Tpi 6 ,Leu 13 , Ψ(CH 2 NH),Leu 14 ]Bn(6-14) [RC-3095] (0.2-1.4 nM) slightly less selective. Analogue #34(PD168368) had the highest affinity for hNMB-receptor (1.32-1.58 nM) and the greatest selectivity (2298-6952-fold) for the hNMB-receptor. These results demonstrate numerous putative hGRP/hNMB-receptor antagonists identified in nonhuman cells and/or animals have agonist activity at the hNMB-receptor, limiting their potential usefulness. However, a number were identified which were potent/selective for human Bn receptors and should be useful for investigating their roles in human physiological/pathophysiological conditions.
Gastroenterology, 2010
Gastroenterology, Volume 138, Issue 5, Pages S-257, May 2010, Authors:Hirotsugu Uehara;Nieves Gon... more Gastroenterology, Volume 138, Issue 5, Pages S-257, May 2010, Authors:Hirotsugu Uehara;Nieves Gonzalez; Samuel A. Mantey; Tomoo Nakagawa; Tatsuro Katsuno; Robert T. Jensen. ...
Gastroenterology, 2008
Gastroenterology, Volume 134, Issue 4, Pages A-709, April 2008, Authors:Nieves Gonzalez; Samuel A... more Gastroenterology, Volume 134, Issue 4, Pages A-709, April 2008, Authors:Nieves Gonzalez; Samuel A. Mantey; Tapas K. Pradhan; Veronica Sancho; Terry W. Moody; David H. Coy; Robert T. Jensen.
Gastroenterology, 2009
BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share ... more BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share 50% homology, are both widely distributed in the GI tract/CNS, but their affinities for their natural occurring agonists [NMB ,GRP]markedly differ. Whereas, the basis of GRP's selectivity for GRPR is well-studied, little is known for NMBR. Previous studies suggested NMBR selectivity for NMB depends primarily on differences in the 3rd extracellular region (EC3) of the two receptors, particularly the presence of alanine (A) instead of isoleucine (I) (position 198,GRPR), histidine (H) instead of glutamine (G)(position 202, GRPR) and a serine (S)(position 215,GRPR) for isoleucine in transmembrane region 5 (TM5). However, the effect of these changes in combination or the molecular basis for the difference of affinity caused by these changes is unknown. AIM: To provide insight into effect of those important amino acids in combination and the molecular basis for differences in EC3/adjacent TM5 affecting NMB affinity for NMBR. METHODS: 3 double mutants (loss or gain of NMB affinity) were made in NMBR or GRPR combining amino acid differences in the EC3/TM5 that alone showed effects. 7 EC3 mutants in [H202]GRPR or 5 [I199]NMBR were made, where H202 or I199 were substituted by single amino acids with different chemical properties. Receptors were transiently expressed in Balb-3T3 cells and affinities determined. RESULTS: The [A198I,H202Q]mutation in GRPR increased 5-fold affinity which, was equal to the substitution of the entire EC3 NMBR domain, and greater than each point mutant alone.
Gastroenterology, 2009
BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share ... more BKG: The mammalian Bombesin receptors [NMBR and Gastrin-Releasing Peptide receptor (GRPR)] share 50% homology, are both widely distributed in the GI tract/CNS, but their affinities for their natural occurring agonists [NMB ,GRP]markedly differ. Whereas, the basis of GRP's selectivity for GRPR is well-studied, little is known for NMBR. Previous studies suggested NMBR selectivity for NMB depends primarily on differences in the 3rd extracellular region (EC3) of the two receptors, particularly the presence of alanine (A) instead of isoleucine (I) (position 198,GRPR), histidine (H) instead of glutamine (G)(position 202, GRPR) and a serine (S)(position 215,GRPR) for isoleucine in transmembrane region 5 (TM5). However, the effect of these changes in combination or the molecular basis for the difference of affinity caused by these changes is unknown. AIM: To provide insight into effect of those important amino acids in combination and the molecular basis for differences in EC3/adjacent TM5 affecting NMB affinity for NMBR. METHODS: 3 double mutants (loss or gain of NMB affinity) were made in NMBR or GRPR combining amino acid differences in the EC3/TM5 that alone showed effects. 7 EC3 mutants in [H202]GRPR or 5 [I199]NMBR were made, where H202 or I199 were substituted by single amino acids with different chemical properties. Receptors were transiently expressed in Balb-3T3 cells and affinities determined. RESULTS: The [A198I,H202Q]mutation in GRPR increased 5-fold affinity which, was equal to the substitution of the entire EC3 NMBR domain, and greater than each point mutant alone.
Gastroenterology, 2008
the fusion fluorescent protein pRFP-LC3 was used as marker. We found that over expression of S100... more the fusion fluorescent protein pRFP-LC3 was used as marker. We found that over expression of S100A10 reduced significantly the recruitment of LC3 induced by VMP1 over expression. In conclusion we were able to find out a group of genes that potentially interact with VMP1 In Vivo and we demonstrated that the interaction VMP1-S100A10 reduces the formation of autophagosomes.
Journal of Molecular Endocrinology, 2005
Several kinases have been implicated in the metabolic response of human and rat myocytes to gluca... more Several kinases have been implicated in the metabolic response of human and rat myocytes to glucagon-like peptide-1 (GLP-1), exendin-4 (Ex-4) and exendin-9 (Ex-9). We have investigated, in isolated rat adipocytes, the changes caused by GLP-1, Ex-4 and Ex-9 compared with those provoked by insulin or glucagon, upon the activity of phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB), p42/44 MAP kinases (MAPKs) and p70s6 kinase (p70s6k), and the participation of these kinases and protein kinase C (PKC) in their action upon 2-deoxy-D-glucose uptake, lipolysis and lipogenesis. The study was conducted in normal rats, and extended to a streptozotocin-induced type-2 diabetic model (STZ-rats). The participation of distinct kinases was estimated by using potential kinase inhibitors, including wortmannin, PD98059, rapamycin, H-7 and RO31-8220. In normal rat adipocytes, GLP-1 and both exendins share with insulin an increasing action upon the activity of all kinases studied (except PKB), PI3K, p44 and p42 MAPKs and possibly PKC, all being required for their stimulating effect upon glucose uptake. Ex-4 and Ex-9, like GLP-1 and insulin, have lipogenic action, while only Ex-4 shares with GLP-1 its lipolytic effect which is antagonized by Ex-9. MAP kinases and PKC seem to have an essential role in the GLP-1 and Ex-4 lipolytic action, as does PI3K in that of Ex-4. An increase in PI3K and MAPKs activity for the lipogenic effect of Ex-4, Ex-9 and GLP-1 are required, and in the case of Ex-4 and Ex-9, a stimulation of p70s6k activity is also needed. In cells from STZ-rats the magnitude of the above parameters was, in general, comparable to that in normal animals, with some exceptions: basal PI3K activity and lipogenesis were higher, GLP-1, Ex-4 and Ex-9 failed to modify basal lipogenesis but increased PKB activity, insulin failed to affect the activity of MAPKs and the insulin-induced glucose uptake was impaired. The impaired insulin effects upon some of the variables in the STZ-rat, distinct from those of GLP-1 and exendins, adds knowledge to the mechanism of the beneficial action of GLP-1 and Ex-4 in diabetic states. V SANCHO and others · Effects of GLP-1 and exendins on adipocytes of normal and diabetic rats