Psychotherapies at a Glance: Consensus Guideline-Recommended Psychotherapies for Adults With Psychiatric Disorders.

Clinical decision making by psychiatrists and informed consent by patients require knowledge of evidence-based psychotherapies (EBPs) and their indications. However, many mental health professionals are not versed in the empirical literature on EBPs or the consensus guideline recommendations derived from this literature. The authors compared rigorous national consensus guidelines for EBP treatment of DSM-defined adult psychiatric disorders-derived from well-conducted randomized controlled trials and meta-analyses and from expert opinions from the United States, United Kingdom, and Canada-to create the Psychotherapies-at-a-Glance tool. Recommended EBPs are cognitive-behavioral therapy, family therapy, contingency management, dialectical behavior therapy, eye movement desensitization reprocessing, interpersonal psychotherapy, mentalization-based treatment, motivational interviewing, peer support, problem-solving therapy, psychoeducation, short-term psychodynamic psychotherapy, and 12-step facilitation. The Psychotherapies-at-a-Glance tool summarizes the indications, rationales, and therapeutic tasks that characterize these differing psychotherapies and psychosocial treatments. The tool is intended for use in clinical teaching, treatment planning, and patient communications.

Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion.

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of ß-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in ß-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve ß cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on ß-cell function and gene expression of factors involved in the maintenance of ß-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.

Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.

Background: Diabetes mellitus is characterized by chronic hyperglycemia with loss of ß-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce ß-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets. Methods and findings: Rat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1ß, IL1ß+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1ß and vitamin D in ß-cells. These include Ri-lnc1, which is enriched in mature ß-cells. Conclusions: Our results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on ß-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic ß-cells and downregulated by IL1ß treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in ß-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.

"It happens to everyone" vs. "You're not a real man": The relationship between intimate communication and men's sexual difficulties.

Sexual difficulties can have negative intrapersonal and interpersonal consequences on both members of a couple, but little is known about how communication in a relationship relates to men's experience of sexual difficulties. We explored the associations among components of intimate communication, men's sexual difficulties, relationship satisfaction, and sexual satisfaction in a sample of men in mixed-gender and same-gender relationships (n = 341). Among all components of intimate communication, sexual communication was most consistently related to indicators of sexual difficulties, relationship satisfaction, and sexual satisfaction. Results generally remained consistent across mixed-gender and same-gender couples, with some exceptions relevant to sexual difficulties.

Changes in lifestyle behaviors during COVID-19 isolation in Argentina: A cross-sectional study.

OBJECTIVE: Our aim was to identify changes in population habits induced by COVID-19 confinement in Argentina. METHODS: An internet-based cross-sectional survey was conducted among adults in Argentina on December 2020, requesting possible changes occurring during the COVID-19 outbreak. It included 26 questions regarding general information (age, gender, location), eating habits, desire/anxiety for food or to eat between meals, weight gain, physical activity, and hours of sleep. We ran a descriptive statistical analysis of changes in habits and lifestyle during the confinement, followed by a logistic regression analysis to explore the relation between these changes and weight gain. Results: Out of 1536 survey participants, 57.1% were female, aged 38.8 ± 13.1 years. Data showed that during the outbreak, people experienced significant changes in food intake, physical activity, nutritional supplement consumption, anxiety, and sleeping disorders. These changes in behavior resulted in an elevated percentage of people (39.7%) that gained weight (average 4.8 ± 2.8 kg). Weight gain was associated with more food consumption (OR: 9.398), increased snacking between meals (OR: 1.536), anxiety about food (OR: 3.180), less practice of physical activity (OR: 0.586) and less consumption of nutritional supplements (OR: 0.762). Conclusions: COVID-19 outbreak was associated with unhealthy lifestyle changes and body weight increase. These adverse side effects could be prevented by active promotion of nutritional advice and physical activity, implementing virtual activities associated with regular mass promotion campaigns.

Interpersonal context and desired emotional closeness in neural response to negative visual stimuli: Preliminary findings.

INTRODUCTION: Emotions typically emerge in interpersonal contexts, but the neural circuitry involved remains insufficiently understood. Two key features of interpersonal contexts are interpersonal interactions (e.g., supportive physical touch serving as a form of social regulation) and interpersonal traits. Social regulation research has predominately focused on fear by using physical threat (i.e., electric shock) as the stimulus. Given that social regulation helps with various negative emotions in the real world, using visual stimuli that elicit negative emotions more broadly would also be beneficial. Differing from trait loneliness-which is related to lower recruitment of social circuitry in negative socioaffective contexts-trait desired emotional closeness is related to adaptive outcomes and may demonstrate an opposite pattern. This study investigated the roles of social regulation and desired emotional closeness in neural response to aversive social images. METHODS: Ten pairs of typically developing emerging adult friends (N = 20; ages 18-25) completed a functional magnetic resonance imaging (fMRI) handholding task. Each friend viewed negative and neutral social images in the scanner under two conditions: (a) holding their friend's hand and (b) having their friend in the room. RESULTS: Handholding attenuated response to aversive social images in a region implicated in emotion and inhibitory control (right dorsal striatum/anterior insula/ventrolateral prefrontal cortex). Desired emotional closeness was positively associated with response to aversive social images (in the no handholding condition) in self and social processing (right ventral posterior cingulate cortex) and somatosensory regions (right postcentral gyrus). DISCUSSION: These findings extend previous research on the roles of interpersonal behaviors and tendencies in neural response to aversive stimuli.

Integrative transcriptomic analysis of pancreatic islets from patients with prediabetes/type 2 diabetes.

AIM: To identify new transcriptomic alterations in pancreatic islets associated with metabolic dysfunctions in people with prediabetes (PD)/type 2 diabetes (T2D). MATERIALS AND METHODS: We collected information from public data repositories T2D related microarray datasets from pancreatic islets. We identified Differential Expressed Genes (DEGs) in non-diabetic (ND) vs people with T2D in each study. To identify relevant DEGs in T2D, we selected those that varied consistently in the different studies for further meta-analysis and functional enrichment analysis. DEGs were also evaluated at the PD stage. RESULTS: A total of seven microarray datasets were collected and analysed to find the DEGs in each study and meta-analysis was performed with 245 ND and 96 T2D cases. We identified 55 transcriptional alterations potentially associated with specific metabolic dysfunctions in T2D. Meta-analysis showed that 87% of transcripts identified as DEGs (48 out of 55) were confirmed as having statistically significant up- or down-modulation in T2D compared to ND. Notably, nine of these DEGs have not been previously reported as dysregulated in pancreatic islets from people with T2D. Consistently, the most significantly enriched pathways were related to the metabolism and/or development/maintenance of ß-cells. Eighteen of the 48 selected DEGs (38%) showed an altered expression in islets from people with PD. CONCLUSIONS: These results provide new evidence to interpret the pathogenesis of T2D and the transition from PD to T2D. Further studies are necessary to validate its potential use for the development/implementation of efficient new strategies for the prevention, diagnosis/prognosis and treatment of T2D.

Social and Non-social Reward Processing and Depressive Symptoms Among Sexual Minority Adolescents.

Sexual minority adolescents (SMA) are more likely to suffer from depression, putatively through experiences of social stress and victimization interfering with processing of social reward. Alterations in neural reward networks, which develop during adolescence, confer risk for the development of depression. Employing both social and monetary reward fMRI tasks, this is the first neuroimaging study to examine function in reward circuitry as a potential mechanism of mental health disparities between SMA and heterosexual adolescents. Eight SMA and 38 heterosexual typically developing adolescents completed self-report measures of depression and victimization, and underwent fMRI during monetary and peer social reward tasks in which they received positive monetary or social feedback, respectively. Compared with heterosexual adolescents, SMA had greater interpersonal depressive symptoms and exhibited blunted neural responses to social, but not monetary, reward in socioaffective processing regions that are associated with depressive symptoms. Specifically, compared with heterosexual adolescents, SMA exhibited decreased activation in the right medial prefrontal cortex, left anterior insula (AI), and right temporoparietal junction (TPJ) in response to being liked. Lower response in the right TPJ was associated with greater interpersonal depressive symptoms. These results suggest that interpersonal difficulties and the underlying substrates of response to social reward (perhaps more so than response to monetary reward) may confer risk for development of depressive symptoms in SMA.

Adolescents' neural response to social reward and real-world emotional closeness and positive affect.

Feeling emotionally close to others during social interactions is a ubiquitous and meaningful experience that can elicit positive affect. The present study integrates functional magnetic resonance imaging (fMRI) and ecological momentary assessment (EMA) to investigate whether neural response to social reward (1) is related to the experience of emotional closeness and (2) moderates the association between emotional closeness and positive affect during and following social interactions. In this study, 34 typically developing adolescents (ages 14-18 years) completed a social-reward fMRI task, a monetary-reward fMRI task, and a 2-week EMA protocol regarding their social and affective experiences. Adolescents with greater right posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ) response to social reward reported greater mean momentary emotional closeness. Neural response to social reward in the right pSTS/TPJ moderated how strongly momentary emotional closeness was associated with both concurrent positive affect and future peak happiness, but in different ways. Although emotional closeness had a significant positive association with concurrent positive affect among adolescents at both high and low right pSTS/TPJ response based on a follow-up simple slopes test, this association was stronger for adolescents with low right pSTS/TPJ response. In contrast, emotional closeness had a significant positive association with future peak happiness among adolescents with high right pSTS/TPJ response, but not among those with low right pSTS/TPJ response. These findings demonstrate the importance of neural response to social reward in key social processing regions for everyday experiences of emotional closeness and positive affect in the context of social interactions.

Prospective assessment of social network quality among depressed mothers treated with brief psychotherapy: The Social Network Quality (SNQ) scales.

OBJECTIVE: Social relationships play important roles in emotional health, and are common targets of psychotherapeutic interventions. To better evaluate social relationship structure and function in the context of psychotherapy trials, this study introduces and psychometrically evaluates the Social Network Quality (SNQ) scales, which supplement the Social Network Index (SNI). The original SNI evaluates social network structure (i.e., extent of participation in diverse social roles and number of social relationships). The SNQ adds two social network quality scales evaluating levels of: (a) positivity/support, and (b) negativity/stress, within and across specific social roles. METHOD: Participants included 168 depressed mothers of psychiatrically-ill children participating in a psychotherapy treatment trial utilizing interpersonal therapy (IPT) and brief supportive therapy (BSP). The SNI, SNQ, and measures of social functioning and psychopathology were collected at baseline and at 3-month intervals over a one-year period. RESULTS: SNQ scores showed meaningful concurrent relationships with measures of social support and interpersonal distress, as well as incremental utility in explaining variance in relationship and mood outcomes above and beyond the SNI. SNQ scores also detected global and relationship-specific changes in social relationship quality following psychotherapy treatment. CONCLUSION: This report demonstrates that SNQ scales reliably assess psychotherapy-induced changes in relationship quality.

VMP1-related autophagy induced by a fructose-rich diet in ß-cells: its prevention by incretins.

The aim of the present study was to demonstrate the role of autophagy and incretins in the fructose-induced alteration of ß-cell mass and function. Normal Wistar rats were fed (3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, ß-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein 1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) or with F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1 and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers (caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituric acid-reactive substances, insulin levels, homoeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) indices. A significant reduction in ß-cell mass was associated with an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression. Chloroquine reduced these changes, suggesting the participation of autophagy in this process. Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting that VMP1-related autophagy is activated in injured ß-cells. Exendin-4 prevented islet-cell damage and autophagy development. VMP1-related autophagy is a reactive process against F-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge could help in the use of autophagy as a potential target for preventing progression from IGT to type 2 diabetes mellitus.

The social regulation of emotion and updating negative contents of working memory.

The social regulation of emotion reduces negative affect and may also help remove negative contents from working memory. The present studies investigated whether the social regulation of emotion (in the form of handholding) altered the ability to update negative contents from working memory and whether a person's level of desired emotional closeness moderated this effect. In each of 2 studies, an unselected sample of undergraduate students completed an emotional working memory task that measured the ability to remove irrelevant information from working memory and a self-report questionnaire measuring their level of desired emotional closeness. In Study 1 (N = 109), the task consisted only of negative images, and each participant performed half of the task while holding someone's hand and the other half while not holding someone's hand. Study 2 (N = 195) included a few changes (e.g., using both negative and neutral images, altering the control condition to consist of holding a stress ball, using a between-participants design, measuring comfort with handholding) to address a few potential alternative explanations. Overall, there appeared to be a better ability to update negative contents of working memory in the handholding condition of each study than the control condition among people with high desired emotional closeness but not among people with low desired emotional closeness. The present findings provide evidence that the social regulation of emotion can facilitate the removal of irrelevant negative contents of working memory. This process may be one way in which supportive relationships protect against psychological distress. (PsycINFO Database Record

The effect of the social regulation of emotion on emotional long-term memory.

Memories for emotional events tend to be stronger than for neutral events, and weakening negative memories can be helpful to promote well-being. The present study examined whether the social regulation of emotion (in the form of handholding) altered the strength of emotional long-term memory. A sample of 219 undergraduate students viewed sets of negative, neutral, and positive images. Each participant held a stress ball while viewing half of the images and held someone's hand while viewing the other half. Participants returned 1 week later to complete a recognition task. Performance on the recognition task demonstrated that participants had lower memory accuracy for negative but not for positive pictures that were shown while they were holding someone's hand compared with when they were holding a stress ball. Although handholding altered the strength of negative emotional long-term memory, it did not down-regulate negative affective response as measured by self-report or facial expressivity. The present findings provide evidence that the social regulation of emotion can help weaken memory for negative information. Given the role of strong negative memories in different forms of psychopathology (e.g., depression, posttraumatic stress disorder), these findings may help better understand how close relationships protect against psychopathology. (PsycINFO Database Record

Examining the contextual and temporal stability of perceptions of emotional utility.

The present research examined the degree to which perceptions of emotional utility are stable across contexts and over time. Self-reported perceptions of emotional utility and actual experience of emotion were measured in two samples of college students. In Study 1, participants were presented with two different types of goals (independent vs. interdependent) and were asked to rate the degree to which they found different types of emotions (e.g., appreciation, pride) useful in each context. In Study 2, participants completed daily online questionnaires in which they responded to questions assessing perceptions of emotional utility and actual affect in relation to personal goals. As predicted, across both samples, perceived utility of specific types of emotions was found to be associated with specific types of goals. Importantly, perceived utility of emotion was also found to be a relatively stable individual difference variable, even after taking into account the actual experience of emotion.

Islet NADPH oxidase activity modulates ß-cell mass and endocrine function in rats with fructose-induced oxidative stress.

BACKGROUND: Islet NADPH oxidase activity is modulated by glucose and other insulin secretagogues and it might be part of the regulatory mechanism of insulin secretion. We studied its modulatory role of islet NADPH oxidase upon ß-cell function in rats with fructose-induced oxidative stress. METHODS: Normal rats were fed for 3weeks with a standard diet, a fructose-rich diet or both diets plus apocynin. We measured plasma glucose, insulin, triacylglycerol and lipid peroxidation levels and the homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-ß indexes, and performed an oral glucose tolerance test. ß-cell volume density and the number of islets per mm(2) were determined by immunomorphometric analysis of the pancreas. Insulin secretion, glucose metabolism, glucokinase and NADPH oxidase activities were studied in islets isolated from each experimental group. RESULTS: Fructose-fed rats had increased plasma triacylglycerol, insulin and lipid peroxidation levels associated with an insulin resistance state; the reactive higher secretion was unable to cope with the increased demand of insulin, leading to an impaired glucose tolerance. They also have a lower number of islets per area unit with a decreased ß-cell volume density. All these alterations were prevented by blocking NADPH oxidase activity with apocynin. CONCLUSION: Fructose-induced changes are partly mediated by modulation of NADPH oxidase activity. GENERAL SIGNIFICANCE: The metabolic dysfunctions and enhanced oxidative stress measured in fructose-fed rats resemble those recorded in human prediabetes; thus, successful strategies employed in this model could be later used to prevent the progression of this state towards type 2 diabetes in human beings.

Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion.

Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-ß-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances ß-cell secretory function and increases ß-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of ß-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a "physiological" positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.

Early detection and staging of spontaneous embryo resorption by ultrasound biomicroscopy in murine pregnancy.

BACKGROUND: Embryo resorption is a major problem in human medicine, agricultural animal production and in conservation breeding programs. Underlying mechanisms have been investigated in the well characterised mouse model. However, post mortem studies are limited by the rapid disintegration of embryonic structures. A method to reliably identify embryo resorption in alive animals has not been established yet. In our study we aim to detect embryos undergoing resorption in vivo at the earliest possible stage by ultra-high frequency ultrasound. METHODS: In a longitudinal study, we monitored 30 pregnancies of wild type C57BI/6 mice using ultra-high frequency ultrasound (30-70 MHz), so called ultrasound biomicroscopy (UBM). We compared the sonoembryology of mouse conceptuses under spontaneous resorption and neighbouring healthy conceptuses and correlated the live ultrasound data with the respective histology. RESULTS: The process of embryo resorption comprised of four stages: first, the conceptus exhibited growth retardation, second, bradycardia and pericardial edema were observed, third, further development ceased and the embryo died, and finally embryo remnants were resorbed by maternal immune cells. In early gestation (day 7 and 8), growth retardation was characterized by a small embryonic cavity. The embryo and its membranes were ill defined or did not develop at all. The echodensity of the embryonic fluid increased and within one to two days, the embryo and its cavity disappeared and was transformed into echodense tissue surrounded by fluid filled caverns. In corresponding histologic preparations, fibrinoid material interspersed with maternal granulocytes and lacunae filled with maternal blood were observed. In later stages (day 9-11) resorption prone embryos were one day behind in their development compared to their normal siblings. The space between Reichert's membrane and inner yolk sac membrane was enlarged The growth retarded embryos exhibited bradycardia and ultimately cessation of heart beat. Corresponding histology showed apoptotic cells in the embryo while the placenta was still intact. In the subsequent resorption process first the embryo and then its membranes disappeared. CONCLUSIONS: Our results provide a temporal time course of embryo resorption. With this method, animals exhibiting embryo resorption can be targeted, enabling the investigation of underlying mechanisms before the onset of total embryo disintegration.

Islet cannabinoid receptors: cellular distribution and biological function.

OBJECTIVES: This study aimed to determine the cellular distribution of islet cannabinoid receptors (CBs) and their involvement in the development of metabolic and hormonal changes in rats fed a fructose-rich diet (F). METHODS: In normal rat islets, we determined CBs (immunofluorescence and retrotranscription-polymerase chain reaction) and glucose-stimulated insulin secretion (GSIS) of isolated islets incubated with the CB1 antagonist rimonabant (R) and/or different CBs agonists. In 3-week F-fed rats, we determined the in vivo effect of R on serum glucose, triglyceride, and insulin levels; homeostasis model assessment for insulin resistance, GSIS, and CBs and insulin receptor substrate gene expression levels (real-time polymerase chain reaction). RESULTS: Cannabinoid receptors appeared exclusively in islet α cells. Whereas different CB agonists enhanced GSIS in normal rat islets, R did not affect it. F rats had higher serum triglyceride and insulin levels and homeostasis model assessment for insulin resistance than control rats; these alterations were prevented by R coadministration. Although R did not correct the increased GSIS observed in F islets, it modulated CBs and insulin receptor substrate gene expression. CONCLUSIONS: Islet CBs would exert an important modulatory role in metabolic homeostasis. Administration of R and F affected islet CB expression and prevented the development of F-induced metabolic impairment. Selective islet CB1 blockers could be useful to prevent/treat the alterations induced by the intake of unbalanced/unhealthy diets.

Islet neogenesis-associated protein (INGAP)-positive cell mass, ß-cell mass, and insulin secretion: their relationship during the fetal and neonatal periods.

OBJECTIVES: To study the chronological appearance of pancreatic islet neogenesis-associated protein (INGAP)-positive cells and its correlation with the increase in ß-cell mass and function in fetal and neonatal rats. METHODS: Normal Wistar rat embryos (E) at gestational days 15, 17, and 19 (E15, E17, E19) and 7-day-old postnatal rats (P7) were humanely killed to determine body and pancreas weight; blood glucose; glucose and arginine-induced insulin secretion; real-time polymerase chain reaction of Pdx1 and Ngn3; quantitative immunomorphometric analysis of ß-cell replication and apoptosis rate, cytokeratin and INGAP cell mass, and Pdx-1- and Ngn3-positive cells. RESULTS: Body and pancreas weight increased with age (P7 > E19 > E17 > E15; P < 0.05). Neonates had higher blood glucose concentrations than embryos (P < 0.05). We recorded a simultaneous and significant age-dependent trend of increase in the number of ß- and Pdx-1-positive cells, ß- and cytokeratin-positive cell mass and ß-cell capacity to release insulin in response to glucose and arginine, and decreased ß-cell apoptotic rate. These changes closely paralleled the increase in INGAP-positive cell mass. CONCLUSIONS: These findings suggest that INGAP exerts a positive modulatory effect on ß-cell mass and its secretory function in fetal and neonatal rats, thus becoming a new component in the multifactorial regulation of such processes.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels.

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca(2+)-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca(2+)-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.