Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets.

An over-activation of the mechanistic target of rapamycin (mTOR) pathway promotes senescence and age-related diseases like type 2 diabetes. Besides, the regenerative potential of pancreatic islets deteriorates with aging. Nevertheless, the role of mTOR on senescence promoted by metabolic stress in islet cells as well as its relevance for electrophysiological aspects is not yet known. Here, we investigated whether parameters suggested to be indicative for senescence are induced in vitro in mouse islet cells by glucotoxicity and if mTOR inhibition plays a protective role against this. Islet cells exhibit a significant increase (~ 76%) in senescence-associated beta-galactosidase (SA-beta-gal) activity after exposure to glucotoxicity for 72 h. Glucotoxicity does not markedly influence p16INK4a protein within 72 h, but p16INK4a levels increase significantly after a 7-days incubation period. mTOR inhibition with a low rapamycin concentration (1 nM) entirely prevents the glucotoxicity-mediated increase of SA-beta-gal and p16INK4a. At the functional level, reactive oxygen species, calcium homeostasis, and electrical activity are disturbed by glucotoxicity, and rapamycin fails to prevent this. In contrast, rapamycin significantly attenuates the insulin hypersecretion promoted by glucotoxicity by modifying the mRNA levels of Vamp2 and Snap25 genes, related to insulin exocytosis. Our data indicate an influence of glucotoxicity on pancreatic islet-cell senescence and a reduction of the senescence markers by mTOR inhibition, which is relevant to preserve the regenerative potential of the islets. Decreasing the influence of mTOR on islet cells exposed to glucotoxicity attenuates insulin hypersecretion, but is not sufficient to prevent electrophysiological disturbances, indicating the involvement of mTOR-independent mechanisms.

Residents Need a Dynamic Approach to Leadership Education: A Qualitative Study.

OBJECTIVE: Leadership is an essential skill for surgeons, but it is not systematically taught in residency. The objective of this study was to explore the current experiences, motivators, and perspectives on leadership training of general surgery residents. DESIGN/SETTING/PARTICIPANTS: Semi-structured focus groups were conducted with 20 general surgery residents at an academic training program. Six in-person sessions (one for each postgraduate year and research) were recorded, transcribed, and de-identified. Data were inductively coded by 2 independent researchers and analyzed thematically. Discrepancies were discussed and resolved through consensus. RESULTS: Participants described developing their leadership skills prior to residency through formal (e.g., job and military) and informal (e.g., extracurricular) experiences. Most reported that leadership development during residency occurred informally (e.g., emulating mentors, trial-and-error). Evolving responsibilities and expectations shaped residents' leadership values: junior residents focused on student and task management and adaptation to new teams; mid-level residents emphasized emotional intelligence and delivery of resident feedback; and senior residents stressed team engagement, inspiring the team, and teaching/mentoring. Major transition periods between residency levels were identified as critical times for leadership training as they allow for self-reflection, motivating residents to participate in a leadership curriculum. Employing level appropriate and immediately applicable content during this time would encourage curriculum attendance and prepare residents for new roles. CONCLUSIONS: There is a lack of formal leadership training in general surgery residency. There is an opportunity to design and implement leadership training that engages surgical residents with level-relevant content and strategies. Transition periods offer optimal timing for maximal curricula uptake.

Defining conditions for effective interdisciplinary care team communication in an open surgical intensive care unit: a qualitative study.

OBJECTIVE: Poor interdisciplinary care team communication has been associated with increased mortality. The study aimed to define conditions for effective interdisciplinary care team communication. DESIGN: An observational cross-sectional qualitative study. SETTING: A surgical intensive care unit in a large, urban, academic referral medical centre. PARTICIPANTS: A total 6 interviews and 10 focus groups from February to June 2021 (N=33) were performed. Interdisciplinary clinicians who cared for critically ill patients were interviewed. Participants included intensivist, transplant, colorectal, vascular, surgical oncology, trauma faculty surgeons (n=10); emergency medicine, surgery, gynaecology, radiology physicians-in-training (n=6), advanced practice providers (n=5), nurses (n=7), fellows (n=1) and subspecialist clinicians such as respiratory therapists, pharmacists and dieticians (n=4). Audiorecorded content of interviews and focus groups were deidentified and transcribed verbatim. The study team iteratively generated the codebook. All transcripts were independently coded by two team members. PRIMARY OUTCOME: Conditions for effective interdisciplinary care team communication. RESULTS: We identified five themes relating to conditions for effective interdisciplinary care team communication in our surgical intensive care unit setting: role definition, formal processes, informal communication pathways, hierarchical influences and psychological safety. Participants reported that clear role definition and standardised formal communication processes empowered clinicians to engage in discussions that mitigated hierarchy and facilitated psychological safety. CONCLUSIONS: Standardising communication and creating defined roles in formal processes can promote effective interdisciplinary care team communication by fostering psychological safety.

A qualitative study of how team characteristics and leadership are associated with information sharing in multidisciplinary intensive care units.

BACKGROUND: Better information sharing in intensive care units has been associated with lower risk-adjusted mortality. This study explored how team characteristics and leadership are associated with information sharing in 4 intensive care units in a single large urban, academic medical center. METHODS: A qualitative study was conducted to understand how team characteristics and leadership are associated with information sharing. Qualitative data were conducted through ethnographic observations. One postdoctoral research fellow and one PhD qualitative researcher conducted nonparticipant observations of a Medical, Surgical, Neurological, and Cardiothoracic intensive care unit morning and afternoon rounds, as well as nurse and resident handoffs from May to September 2021. Field notes of observations were thematically analyzed using deductive reasoning anchored to the Edmondson Team Learning Model. This study included nurses, physicians (ie, intensivists, surgeons, fellows, and residents), medical students, pharmacists, respiratory therapists, dieticians, physical therapists, physician assistants, and nurse practitioners. RESULTS: We conducted 50 person-hours of observations involving 148 providers. Three themes emerged from the qualitative analysis: (1) team leaders used variable leadership techniques to involve team members in discussions for information sharing related to patient care, (2) predefined tasks for team members allowed them to prepare for effective information sharing during intensive care unit rounds, and (3) a psychologically safe environment allowed team members to participate in discussions for information sharing related to patient care. CONCLUSION: Inclusive team leadership is foundational in creating a psychologically safe environment for effective information sharing.

Molecular changes underlying pulmonary emphysema and chronic bronchitis in Chronic Obstructive Pulmonary Disease: An updated review.

The aim of this review is to update and synthesize the molecular mechanisms that lead to the heterogeneous effect on tissue remodeling observed in the two most important clinical phenotypes of chronic obstructive pulmonary disease (COPD), pulmonary emphysema (PE) and chronic bronchitis (CB). Clinical and experimental evidence suggests that this heterogeneous response to promote PE, CB, or both, is related to differentiated genetic, epigenetic, and molecular conditions. Specifically, a tendency toward PE could be related to a variant in the DSP gene, SIRT1 downregulation, macrophage polarization to M1, as well as the involvement of the noncanonical Wnt5A signaling pathway, among other alterations. Additionally, in advanced stages of COPD, PE development is potentiated by dysregulations in autophagy, which promotes senescence and subsequently cell apoptosis, through exacerbated inflammasome activation and release of caspases. On the other hand, CB or the pro-fibrotic phenotype could be potentiated by the downregulated activity of HDAC2, the activation of the TGF-ß/Smad or Wnt/ß-catenin signaling pathways, macrophage polarization to M2, upregulation of TIMP-1, and/or the presence of the epithelial-mesenchymal transition (EMT) mechanism. Interestingly, the upregulated activity of MMPs, especially MMP-9, is widely involved in the development of both phenotypes. Furthermore, MMP-9 and MMP-12 enhance the severity, perpetuation, and exacerbation of COPD, as well as the development of autoimmunity in this disease.

Maize Flavonoid Biosynthesis, Regulation, and Human Health Relevance: A Review.

Maize is one of the most important crops for human and animal consumption and contains a chemical arsenal essential for survival: flavonoids. Moreover, flavonoids are well known for their beneficial effects on human health. In this review, we decided to organize the information about maize flavonoids into three sections. In the first section, we include updated information about the enzymatic pathway of maize flavonoids. We describe a total of twenty-one genes for the flavonoid pathway of maize. The first three genes participate in the general phenylpropanoid pathway. Four genes are common biosynthetic early genes for flavonoids, and fourteen are specific genes for the flavonoid subgroups, the anthocyanins, and flavone C-glycosides. The second section explains the tissue accumulation and regulation of flavonoids by environmental factors affecting the expression of the MYB-bHLH-WD40 (MBW) transcriptional complex. The study of transcription factors of the MBW complex is fundamental for understanding how the flavonoid profiles generate a palette of colors in the plant tissues. Finally, we also include an update of the biological activities of C3G, the major maize anthocyanin, including anticancer, antidiabetic, and antioxidant effects, among others. This review intends to disclose and integrate the existing knowledge regarding maize flavonoid pigmentation and its relevance in the human health sector.

In Vivo Healthy Benefits of Galacto-Oligosaccharides from Lupinus albus (LA-GOS) in Butyrate Production through Intestinal Microbiota.

Animal digestive systems host microorganism ecosystems, including integrated bacteria, viruses, fungi, and others, that produce a variety of compounds from different substrates with healthy properties. Among these substrates, α-galacto-oligosaccharides (GOS) are considered prebiotics that promote the grow of gut microbiota with a metabolic output of Short Chain Fatty Acids (SCFAs). In this regard, we evaluated Lupinus albus GOS (LA-GOS) as a natural prebiotic using different animal models. Therefore, the aim of this work was to evaluate the effect of LA-GOS on the gut microbiota, SCFA production, and intestinal health in healthy and induced dysbiosis conditions (an ulcerative colitis (UC) model). Twenty C57BL/6 mice were randomly allocated in four groups (n = 5/group): untreated and treated non-induced animals, and two groups induced with 2% dextran sulfate sodium to UC with and without LA-GOS administration (2.5 g/kg bw). We found that the UC treated group showed a higher goblet cell number, lower disease activity index, and reduced histopathological damage in comparison to the UC untreated group. In addition, the abundance of positive bacteria to butyryl-CoA transferase in gut microbiota was significantly increased by LA-GOS treatment, in healthy conditions. We measured the SCFA production with significant differences in the butyrate concentration between treated and untreated healthy groups. Finally, the pH level in cecum feces was reduced after LA-GOS treatment. Overall, we point out the in vivo health benefits of LA-GOS administration on the preservation of the intestinal ecosystem and the promotion of SCFA production.

Lupin γ-conglutin protects against cell death induced by oxidative stress and lipotoxicity, but transiently inhibits in vitro insulin secretion by increasing KATP channel currents.

Lupin γ-conglutin beneficially modulates glycemia, but whether it protects against oxidative and lipotoxic damage remains unknown. Here, we studied the effects of γ-conglutin on cell death provoked by hydrogen peroxide and palmitate in HepG2 hepatocytes and insulin-producing MIN6 cells, and if a modulation of mitochondrial potential and reactive oxygen species (ROS) levels was involved. We also investigated how γ-conglutin influences insulin secretion and electrical activity of ß-cells. The increased apoptosis of HepG2 cells exposed to hydrogen peroxide was prevented by γ-conglutin, and the viability and ROS content in γ-conglutin-treated cells was similar to that of non-exposed cells. Additionally, γ-conglutin partially protected MIN6 cells against hydrogen peroxide-induced death. This was associated with a marked reduction in ROS. No significant changes were found in the mitochondrial potential of γ-conglutin-treated cells. Besides, we observed a partial protection against lipotoxicity only in hepatocytes. Unexpectedly, we found a transient inhibition of insulin secretion, plasma membrane hyperpolarization, and higher KATP channel currents in ß-cells treated with γ-conglutin. Our data show that γ-conglutin protects against cell death induced by oxidative stress or lipotoxicity by decreasing ROS and might also indicate that γ-conglutin promotes a ß-cell rest, which could be useful for preventing ß-cell exhaustion in chronic hyperglycemia.

Glucokinase activation as antidiabetic therapy: effect of nutraceuticals and phytochemicals on glucokinase gene expression and enzymatic activity.

Diabetes represents an important public health problem. Recently, new molecular targets have been identified and exploited to treat this disease. Due to its pivotal role in glucose homeostasis, glucokinase (GCK) is a promising target for the development of novel antidiabetic drugs; however, pharmacological agents that modulate GCK activity have been linked to undesirable side-effects, limiting its use. Interestingly, plants might be a valuable source of new therapeutic compounds with GCK-activating properties and presumably no adverse effects. In this review, we describe biochemical characteristics related to the physiological and pathological importance of GCK, as well as the mechanisms involved in its regulation at different molecular levels. Posteriorly, we present a compendium of findings supporting the potential use of nutraceuticals and phytochemicals in the management of diabetes through modulation of GCK expression and activity. Finally, we propose critical aspects to keep in mind when designing experiments to evaluate GCK modulation properly.

Effect of the acute and chronic administration of Lupinus albus ß-conglutin on glycaemia, circulating cholesterol, and genes potentially involved.

Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for dysglycaemia management. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including ß-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of ß-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. We analysed the liver transcriptome modulation exerted by ß-conglutin in diabetes-induced rats using DNA microarrays to scout for potential molecular targets and pathways involved in this biological response. The acute administration of ß-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of ß-conglutin. Total cholesterol was significantly lower at the end of the experimental period (-21.8 %, p = 0.039). The microarray and gene ontology analyses revealed several targets and pathways potentially modulated by ß-conglutin treatment, including a possible down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that ß-conglutin may help manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of ß-conglutin.

Molecular inflammation and oxidative stress are shared mechanisms involved in both myocardial infarction and periodontitis.

BACKGROUND AND OBJECTIVE: Our aims were to improve the understanding of the pathogenic relationship between cardiovascular diseases and periodontitis and to generate new perspectives in the prevention and treatment of acute myocardial infarction (AMI) and periodontitis. The present study evaluates possible differences in inflammation, oxidative stress, and autophagy markers among subject suffering AMI, periodontitis, or both, to explore possible common pathogenic mechanisms. MATERIAL AND METHODS: A total of 260 subjects were enrolled in the study: 106 subjects that survived to a first AMI (AMI group) and 154 subjects had no cardiac events in their clinical record (control group). A questionnaire was used to assess age, height, weight, blood pressure, and heart rate. The clinical probing depth, clinical attachment loss, number of remaining teeth, and average number of sites with bleeding on probing were assessed. Lipid peroxidation and protein levels of phosphorylated AMP-activated protein kinase (p-AMPK) and microtubule-associated proteins 1A/1B-light chain 3-II (LC3-II) were determined in isolated peripheral blood mononuclear cells by thiobarbituric acid reactive substances (TBARS) assay and Western blot, respectively. Plasma levels of interleukin-1ß were determined using a commercial ELISA kit. All the obtained variables were compared between subjects suffering an AMI with or without periodontitis and control subject periodontal healthy or with periodontitis. RESULTS: A higher proportion of subjects suffering AMI + periodontitis than only AMI (without periodontitis) was found. Higher levels of TBARS were found in subjects with periodontitis than in subjects without periodontitis in both AMI and control subjects. Positive correlations between IL-1ß levels and TBARS and between IL-1ß levels and LC3-II were found only in control subjects. CONCLUSION: Results from the present study are consistent with the suggestion of periodontitis as a potential risk factor for AMI. Periodontitis association with circulating lipid peroxides in both AMI and control subjects were found. The absence of differences in IL-1ß levels between AMI subjects (only AMI vs AMI + periodontitis) suggests that oxidative stress could be the main pathogenic link between AMI and periodontitis.

Lupin gamma conglutin protein: effect on Slc2a2, Gck and Pdx-1 gene expression and GLUT2 levels in diabetic rats

ABSTRACT Recently, lupin seed (Lupinus albus L., Fabaceae) products have emerged as a functional food due to their nutritional and health benefits. Numerous reports have demonstrated the hypoglycemic effects of lupin's gamma conglutin protein; nonetheless, its mechanism of action remains elusive. To understand the role of this protein on glucose metabolism, we evaluated the effect of administering L. albus' gamma conglutin on Slc2a2, Gck, and Pdx-1 gene expression as well as GLUT2 protein tissue levels in streptozotocin-induced diabetic rats. While consuming their regular diet, animals received a daily gamma conglutin dose (120 mg/kg per body weight) for seven consecutive days. Serum glucose levels were measured at the beginning and at the end of the experimental period. At the end of the trial, we quantified gene expression in pancreatic and hepatic tissues as well as GLUT2 immunopositivity in Langerhans islets. Gamma conglutin administration lowered serum glucose concentration by 17.7%, slightly increased Slc2a2 and Pdx-1 mRNA levels in pancreas, up-regulated Slc2a2 expression in the liver, but it had no effect on hepatic Gck expression. After gamma conglutin administration, GLUT2 immunopositivity in Langerhans islets of diabetic animals resembled that of healthy rats. In conclusion, our results indicate that gamma conglutin up-regulates Slc2a2 gene expression in liver and normalizes GLUT2 protein content in pancreas of streptozotocin-induced rats.

Insulin glargine affects the expression of Igf-1r, Insr, and Igf-1 genes in colon and liver of diabetic rats.

OBJECTIVES: The mitogenic effect of the analogous insulin glargine is currently under debate since several clinical studies have raised the possibility that insulin glargine treatment has a carcinogenic potential in different tissues. This study aimed to evaluate the Igf-1r, Insr, and Igf-1 gene expression in colon and liver of streptozotocin-induced diabetic rats in response to insulin glargine, neutral protamine Hagedorn (NPH) insulin, and metformin treatments. MATERIALS AND METHODS: Male Wistar rats were induced during one week with streptozotocin to develop Type 2 Diabetes (T2D) and then randomly distributed into four groups. T2D rats included in the first group received insulin glargine, the second group received NPH insulin, the third group received metformin; finally, untreated T2D rats were included as the control group. All groups were treated for seven days; after the treatment, tissue samples of liver and colon were obtained. Quantitative PCR (qPCR) was performed to analyze the Igf-1r, Insr and Igf-1 gene expression in each tissue sample. RESULTS: The liver tissue showed overexpression of the Insr and Igf-1r genes (P>0.001) in rats treated with insulin glargine in comparison with the control group. Similar results were observed for the Insr gene (P>0.011) in colonic tissue of rats treated with insulin glargine. CONCLUSION: These observations demonstrate that insulin glargine promote an excess of insulin and IGF-1 receptors in STZ-induced diabetic rats, which could overstimulate the mitogenic signaling pathways.

Xylem resistance to embolism: presenting a simple diagnostic test for the open vessel artefact.

Xylem vulnerability to embolism represents an essential trait for the evaluation of the impact of hydraulics in plant function and ecology. The standard centrifuge technique is widely used for the construction of vulnerability curves, although its accuracy when applied to species with long vessels remains under debate. We developed a simple diagnostic test to determine whether the open-vessel artefact influences centrifuge estimates of embolism resistance. Xylem samples from three species with differing vessel lengths were exposed to less negative xylem pressures via centrifugation than the minimum pressure the sample had previously experienced. Additional calibration was obtained from non-invasive measurement of embolism on intact olive plants by X-ray microtomography. Results showed artefactual decreases in hydraulic conductance (k) for samples with open vessels when exposed to a less negative xylem pressure than the minimum pressure they had previously experienced. X-Ray microtomography indicated that most of the embolism formation in olive occurs at xylem pressures below -4.0 MPa, reaching 50% loss of hydraulic conductivity at -5.3 MPa. The artefactual reductions in k induced by centrifugation underestimate embolism resistance data of species with long vessels. A simple test is suggested to avoid this open vessel artefact and to ensure the reliability of this technique in future studies.

Lupinus albus Conglutin Gamma Modifies the Gene Expressions of Enzymes Involved in Glucose Hepatic Production In Vivo.

Lupinus albus seeds contain conglutin gamma (Cγ) protein, which exerts a hypoglycemic effect and positively modifies proteins involved in glucose homeostasis. Cγ could potentially be used to manage patients with impaired glucose metabolism, but there remains a need to evaluate its effects on hepatic glucose production. The present study aimed to analyze G6pc, Fbp1, and Pck1 gene expressions in two experimental animal models of impaired glucose metabolism. We also evaluated hepatic and renal tissue integrity following Cγ treatment. To generate an insulin resistance model, male Wistar rats were provided 30% sucrose solution ad libitum for 20 weeks. To generate a type 2 diabetes model (STZ), five-day-old rats were intraperitoneally injected with streptozotocin (150 mg/kg). Each animal model was randomized into three subgroups that received the following oral treatments daily for one week: 0.9% w/v NaCl (vehicle; IR-Ctrl and STZ-Ctrl); metformin 300 mg/kg (IR-Met and STZ-Met); and Cγ 150 mg/kg (IR-Cγ and STZ-Cγ). Biochemical parameters were assessed pre- and post-treatment using colorimetric or enzymatic methods. We also performed histological analysis of hepatic and renal tissue. G6pc, Fbp1, and Pck1 gene expressions were quantified using real-time PCR. No histological changes were observed in any group. Post-treatment G6pc gene expression was decreased in the IR-Cγ and STZ-Cγ groups. Post-treatment Fbp1 and Pck1 gene expressions were reduced in the IR-Cγ group but increased in STZ-Cγ animals. Overall, these findings suggest that Cγ is involved in reducing hepatic glucose production, mainly through G6pc inhibition in impaired glucose metabolism disorders.

Is the relationship between mast-seeding and weather in oaks related to their life-history or phylogeny?

Although the functional basis of variable and synchronous seed production (masting behavior) has been extensively investigated, only recently has attention been focused on the proximate mechanisms driving this phenomenon. We analyzed the relationship between weather and acorn production in 15 species of oaks (genus Quercus) from three geographic regions on two continents, with the goals of determining the extent to which similar sets of weather factors affect masting behavior across species and to explore the ecological basis for the similarities detected. Lag-1 temporal autocorrelations were predominantly negative, supporting the hypothesis that stored resources play a role in masting behavior across this genus, and we were able to determine environmental variables correlating with acorn production in all but one of the species. Standard weather variables outperformed "differential-cue" variables based on the difference between successive years in a majority of species, which is consistent with the hypothesis that weather is linked directly to the proximate mechanism driving seed production and that masting in these species is likely to be sensitive to climate change. Based on the correlations between weather variables and acorn production, cluster analysis failed to generate any obvious groups of species corresponding to phylogeny or life-history. Discriminant function analyses, however, were able to identify the phylogenetic section to which the species belonged and, controlling for phylogeny, the length of time species required to mature acorns, whether they were evergreen or deciduous, and, to a lesser extent, the geographic region to which they are endemic. These results indicate that similar proximate mechanisms are driving acorn production in these species of oaks, that the environmental factors driving seed production in oaks are to some extent phylogenetically conserved, and that the shared mechanisms driving acorn production result in some degree of synchrony among coexisting species in a way that potentially enhances predator satiation, at least when they have acorns requiring the same length of time to mature.

Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression.

The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg/kg body weight). In the presence of 15 mmol/L glucose, insulin secretion was significantly elevated by 0.5 mmol/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca(2+) action potentials. Determination of the current through ATP-dependent K⁺ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of 1 mmol/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.

Why is seed production so variable among individuals? A ten-year study with oaks reveals the importance of soil environment.

Mast-seeding species exhibit not only a large inter-annual variability in seed production but also considerable variability among individuals within the same year. However, very little is known about the causes and consequences for population dynamics of this potentially large between-individual variability. Here, we quantified seed production over ten consecutive years in two Mediterranean oak species - the deciduous Quercus canariensis and the evergreen Q. suber - that coexist in forests of southern Spain. First, we calibrated likelihood models to identify which abiotic and biotic variables best explain the magnitude (hereafter seed productivity) and temporal variation of seed production at the individual level (hereafter CVi), and infer whether reproductive effort results from the available soil resources for the plant or is primarily determined by selectively favoured strategies. Second, we explored the contribution of between-individual variability in seed production as a potential mechanism of satiation for predispersal seed predators. We found that Q. canariensis trees inhabiting moister and more fertile soils were more productive than those growing in more resource-limited sites. Regarding temporal variation, individuals of the two studied oak species inhabiting these resource-rich environments also exhibited larger values of CVi. Interestingly, we detected a satiating effect on granivorous insects at the tree level in Q. suber, which was evident in those years where between-individual variability in acorn production was higher. These findings suggest that individual seed production (both in terms of seed productivity and inter-annual variability) is strongly dependent on soil resource heterogeneity (at least for one of the two studied oak species) with potential repercussions for recruitment and population dynamics. However, other external factors (such as soil heterogeneity in pathogen abundance) or certain inherent characteristics of the tree might be also involved in this process.

Administration of Lupinus albus gamma conglutin (Cγ) to n5 STZ rats augmented Ins-1 gene expression and pancreatic insulin content.

Several studies support the health-promoting benefits of lupins, particularly lupin proteins. It has been demonstrated that Lupinus albus gamma conglutin (Cγ) protein lowered blood glucose levels; thus, Cγ showed promise as a new anti-diabetic compound for type 2 diabetes (T2D) treatment. The aim of this study was to evaluate the effect of Cγ on Ins-1 gene expression and on pancreatic insulin content in streptozotocin-mediated diabetic rats. Cγ was isolated from Lupinus albus seeds. Its identification was confirmed with polyacrylamide gel electrophoresis under native and denaturing conditions. We used streptozotocin (STZ) to induce T2D on the 5th day of life of newborn male Wistar rats (n5-STZ). After 20 weeks post-induction, these animals (glycemia > 200 mg/dL) were randomly assigned to three groups that received the following one-week treatments: vehicle, 0.90% w/v NaCl (n5 STZ-Ctrl); glibenclamide, 10 mg/kg (n5 STZ-Glib); or Cγ, 120 mg/kg (n5 STZ-Cγ). Glucose and insulin levels were measured before and after treatment. Ins-1 gene expression was quantified using real time polymerase chain reaction and the pancreatic insulin content was evaluated with immunohistochemistry. Post-treatment, the n5 STZ-Cγ and n5 STZ-Glib groups showed reductions in glucose, increments in serum insulin, and increases in Ins-1 gene expression and beta cell insulin content compared to the n5 STZ-Ctrl group. The results showed that Cγ had beneficial effects on Ins-1 gene expression and pancreatic insulin content. These biological effects of Cγ strengthen its promising potential as a nutraceutical and/or new agent for controlling hyperglycemia.

Reduction of lns-1 gene expression and tissue insulin levels in n5-STZ rats.

OBJECTIVE: The high global incidence of type 2 diabetes has challenged researchers to establish animal models that resemble the chronic stage observed in type 2 diabetes patients. One such model is induced by neonatal streptozotocin (n-STZ) administration to rat pups at 0, 2, or 5 days after birth. In this study, we assessed lns-1 gene expression and tissue insulin levels as well as serum concentration of glucose and insulin, insulin resistance, and histological changes of the islets of Langerhans in n5-STZ rats after 20-weeks post-induction. METHODS: Wistar rat pups were randomly distributed into a control group and a streptozotocin-induced group. Experimental induction involved a single intraperitoneal injection of streptozotocin (150 mg/kg) into neonates at five days after birth. RESULTS: At 20 weeks post-induction, streptozotocin-induced rats exhibited increased serum glucose levels, reduced serum insulin levels, impaired glucose metabolism and insulin resistance compared to control rats. Histologically, streptozotocin-induced rats exhibited atrophic islets, vacuolization, and significantly fewer insulin-positive cells. lns-1 gene expression was significantly decreased in n5-STZ rats in comparison to the control group. CONCLUSION: Our findings support that the n5-STZ model 20 weeks post-induction represents an appropriate experimental tool to study T2D and to evaluate novel therapeutic agents and targets that involve insulin gene expression and secretion, as well as complications caused by chronic diabetes.