Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes.

Few studies in Asian populations have analyzed how glucagon secretion is affected by ingested glucose, proteins or lipids, individually. To investigate the fluctuations of glucagon secretion after the intake of each of these nutrients, 10 healthy volunteers underwent oral loading tests using each of glucose, proteins and lipids, and blood levels of glucose, insulin and glucagon were measured every 30 min for 120 min. Whereas glucagon secretion was suppressed and minimally affected by oral glucose intake and lipid intake, respectively, oral protein intake robustly increased glucagon secretion, as well as insulin secretion. Further studies are needed to elucidate the mechanism by which protein loading increases glucagon secretion.

Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding.

G protein-coupled receptor (GPR) 120 is expressed in enteroendocrine cells secreting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP), and cholecystokinin (CCK). Although GPR120 signaling in adipose tissue and macrophages has been reported to ameliorate obesity and insulin resistance in a high long-chain triglyceride (LCT) diet, intestine-specific roles of GPR120 are unclear. To clarify the metabolic effect of GPR120 in the intestine, we generated intestine-specific GPR120-knockout (GPR120int-/-) mice. In comparison with floxed GPR120 (WT) mice, GPR120int-/- mice exhibited reduced GIP secretion and CCK action without change of insulin, GLP-1, or peptide YY (PYY) secretion after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed a mild reduction of body weight and substantial amelioration of insulin resistance and fatty liver. Moreover, liver and white adipose tissue (WAT) of GPR120int-/-mice exhibited increased Akt phosphorylation and reduced gene expression of suppressor of cytokine signaling (SOCS) 3, which inhibits insulin signaling. In addition, gene expression of inflammatory cytokines in WAT and lipogenic molecules in liver were reduced in GPR120int-/- mice. These findings suggest that inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-LCT diet feeding.NEW & NOTEWORTHY We generated novel intestine-specific GPR120-knockout (GPR120int-/-) mice and investigated the metabolic effect of GPR120 in the intestine. GPR120int-/- mice exhibited a reduction of GIP secretion and CCK action after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed mild improvement in obesity and marked amelioration of insulin resistance and hepatic steatosis. Our results indicate an important role of intestinal GPR120 on insulin resistance and hepatic steatosis.

The Effect of Dextrose or Protein Ingestion on Circulating Growth Differentiation Factor 15 and Appetite in Older Compared to Younger Women.

Growth differentiation factor 15 (GDF15) is a stress signal that can be induced by protein restriction and is associated with reduced food intake. Anorexia of aging, insufficient protein intake as well as high GDF15 concentrations often occur in older age, but it is unknown whether GDF15 concentrations change acutely after meal ingestion and affect appetite in older individuals. After an overnight fast, appetite was assessed in older (n = 20; 73.7 ± 6.30 years) and younger (n = 20; 25.7 ± 4.39 years) women with visual analogue scales, and concentrations of circulating GDF15 and glucagon-like peptide-1 (GLP-1) were quantified before and at 1, 2 and 4 h after ingestion of either dextrose (182 kcal) or a mixed protein-rich meal (450 kcal). In response to dextrose ingestion, appetite increased in both older and younger women, whereas GDF15 concentrations increased only in the older group. In older women, appetite response was negatively correlated with the GDF15 response (rho = -0.802, p = 0.005). Following high-protein ingestion, appetite increased in younger women, but remained low in the old, while GDF15 concentrations did not change significantly in either age group. GLP-1 concentrations did not differ between age groups or test meals. In summary, acute GDF15 response differed between older and younger women. Associations of postprandial appetite and GDF15 following dextrose ingestion in older women suggest a reduced appetite response when the GDF15 response is high, thus supporting the proposed anorectic effects of high GDF15 concentrations.

Paradoxical GH increase during oral glucose load may predict overall remission in acromegalic patients.

BACKGROUND: The nadir growth hormone (nGH) during the oral glucose tolerance test (OGTT) is the gold standard method for diagnosing acromegaly. A paradoxical growth hormone (GH) response to oral glucose (OG) in acromegaly can be observed. The role of the paradoxical GH response on how the patients with acromegaly respond to the treatment has been addressed in few studies. The aim of this study was to investigate the association between glucose-dependent growth hormone results and and the responses of acromegalic patients to surgical and/or medical therapy following surgery. MATERIAL AND METHODS: This retrospective cohort study included patients with acromegaly who underwent surgery (n = 189) or received primary medical treatment (n = 9). The mean age was 50.44 ± 12.81 years (M/F: 84/114). The patients were grouped into paradoxical (GH-P) and non-paradoxical (GH-nP) according to GH response to OG and were compared in terms of clinical and pathological features, pituitary tumor size, invasiveness, biochemical profiles, and how they responded to the treatment. RESULTS: The mean age, gender distribution, and basal tumor diameter were all similar in both groups (p > 0.05). The GH-P group had a higher remission rate in response to medical therapy followed by surgery (83% vs. 55%; p = 0.026). Although a higher surgical remission rate in favor of GH-P was observed, it did not reach statistical significance (63% vs. 48%; p = 0.059). Overall treatment response rates were also higher in the GH-P group compared to the GH-nP group (89% vs. 71%; p = 0.005). CONCLUSION: A paradoxical GH response to OG load may help to predict the response to medical treatment in patients with acromegaly.

Effects of mammalian blood with different glucose levels on reproduction, growth and survival of the southern medicinal leech, Hirudo verbana Carena, 1820.

Medicinal leeches are generally fed using pure mammalian blood. In the present study reproduction, growth and survival of medicinal leeches (Hirudo spp.) fed by mammalian blood with modified glucose level were investigated for the first time. Leeches were fed by cattle blood in a final glucose level of 152 mg/dL (control group; Glucose-free), 200 mg/dL (G200 group), 300 mg/dL (G300 group), 500 mg/dL (G500 group), 750 mg/dL (G750 group), 1000 mg/dL (G1000 group), 2500 mg/dL (G2500 group) and 5000 mg/dL (G5000 group) with the addition of D-Glucose Monohydrate. Greatest growth performance was determined in the G2500 group with a specific growth rate of 2.34% (final body weight: 10.37 ± 3.86 g) (P < 0.05). A quadratic increase was observed in the body weight values of the leeches depending on the glucose dose (Plinear and Pquadratic < 0.05). The greatest survival and gravidity rates were 89% and 38%, respectively, in the G750 group (P < 0.05). The increased glucose level caused a sharp decrease in the survival and gravidity rates of leeches. The glucose level did not significantly effected the cocoon and offspring productivity (P > 0.05). According to the broken line model, optimum glucose levels based on growth, survival rate and gravidity rate were 2461 mg/dL, 750.0 mg/dL and 749.9 mg/dL, respectively. The study showed that, although the optimum growth performance was obtained in the G2500 group, blood with glucose level of 750 mg/dL should be used for profitable medicinal leech culture considering survival and gravidity rates.

Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway.

BACKGROUND: High glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown. METHODS: Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways. RESULTS: We found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose. CONCLUSIONS: The present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.

El consumo regular de un caldo funcional enriquecido con fosfofructooligosacáridos aumenta los niveles de las hormonas relacionadas con la saciedad en las personas sanas. Ensayo clínico aleatorizado y controlado / Regular consumption of a functional broth enriched with phospho-fructooligosaccharides increases the levels of hormones related to satiety in healthy people. A randomized, controlled clinical trial

Introducción: el exceso de peso representa un problema de salud pública debido a los factores de riesgo asociados. El sedentarismo, una alimentación inadecuada o una disminución de la sensación de saciedad son algunas de sus causas. Objetivos: evaluar las propiedades saciantes del consumo de un caldo ibérico funcional enriquecido con fosfofructooligosacáridos (FOS) en personas sanas a través de la concentración plasmática de las hormonas involucradas en el apetito. Material y métodos: ensayo clínico nutricional, agudo, cruzado, aleatorizado, doble ciego y controlado, llevado a cabo en 18 participantes aleatorizados en dos secuencias de tratamiento (caldo funcional (CF) compuesto de 5,6 g de FOS/100 g y caldo de control (CC), con 0,4 g de maltodextrina/100 g) con 14 días de lavado entre ellas. Se midieron parámetros relacionados con la saciedad (glucosa, insulina, leptina, ghrelina, GLP-1, PYY) y escalas analógicas visuales (EAV). Resultados: el porcentaje de grasa corporal disminuyó en los que tomaron el CF (-0,15 ± 0,32 vs. 0,09 ± 0,52) (p < 0,05). La concentración de leptina fue superior con el CF (p < 0,001), mostrándose dicho aumento en los tiempos -30 (p < 0,001), 0 (p < 0,001), 30 (p = 0,026) y 120 (p = 0,049) con respecto al CC. Las áreas bajo la curva (AUC) de GLP-1 (p = 0,0033) y PYY (p = 0,022) fueron superiores con el CF en comparación con el CC. Conclusión: el consumo de un caldo ibérico enriquecido con FOS mejora la concentración plasmática de las hormonas involucradas en el control de la saciedad y reduce la cantidad de grasa corporal. Dichos resultados podrían tener efectos beneficiosos para la prevención y el tratamiento del exceso de peso corporal (AU)

Introduction: excess weight represents a public health problem due to its associated risk factors. A sedentary lifestyle, an inadequate diet or a decrease in the feeling of satiety are some of the causes. Objetives: to evaluate the satiating properties of the consumption of a functional Iberian broth enriched with phospho-fructooligosaccharides (FOS) in healthy people through the plasma concentration of hormones involved in appetite. Material and methods: acute, crossover, randomized, double-blind and controlled nutritional clinical trial carried out in 18 randomized participants in two treatment sequences (functional broth (CF), composed of 5.6 g POS/100 g and control broth (CC), with 0.4 g of maltodextrin/100 g) with 14 days of washing in between. Satiety-related parameters (glucose, insulin, leptin, ghrelin, GLP-1, PYY) and visual analog scales (VAS) were measured. Results: the percentage of body fat decreased in those who took the CF (-0.15 ± 0.32 vs 0.09 ± 0.52) (p < 0.05). Leptin concentration was higher with CF (p < 0.001), which was shown at time points -30 (p < 0.001), 0 (p < 0.001), 30 (p = 0.026) and 120 (p = 0.049) when compared to CC. The areas under the curve (AUC) for GLP-1 (p = 0.0033) and PYY (p = 0.022) were higher for CF as compared to CC. Conclusion: consumption of an Iberian broth enriched with POS improves the plasma concentration of hormones involved in the control of satiety, and reduces the amount of body fat. This result could have beneficial effects for the prevention and treatment of overweight (AU)

Hsa_circ_0037128 aggravates high glucose-induced podocytes injury in diabetic nephropathy through mediating miR-31-5p/KLF9.

BACKGROUND: Circular RNA is a key regulator involved in the progression of many human diseases including diabetic nephropathy (DN). However, the role and mechanism of hsa_circ_0037128 in the occurrence and development of DN remains to be explored. METHODS: High glucose (HG)-induced podocytes were used to construct in vitro DN models. The expression of hsa_circ_0037128, microRNA (miR)-31-5p, and Kruppel-like factor 9 (KLF9) was determined using quantitative real-time polymerase chain reaction. The viability and apoptosis of podocytes was measured using cell counting kit 8 assay and flow cytometry. Western blot analysis was performed to examine the protein levels of apoptosis markers and KLF9 in podocytes. Inflammation factors were detected by ELISA assay, and oxidative stress markers were assessed by corresponding Assay Kits. In addition, the interaction between miR-31-5p and hsa_circ_0037128 or KLF9 was verified using dual-luciferase reporter assay and RIP assay. RESULTS: Our data suggested that hsa_circ_0037128 was highly expressed in DN patients and HG-induced podocytes. In HG-induced podocytes, hsa_circ_0037128 knockdown could alleviate HG-induced podocytes injury. In the term of mechanism, hsa_circ_0037128 could sponge miR-31-5p to upregulate KLF9. MiR-31-5p inhibitor could reverse the negative regulation of hsa_circ_0037128 silencing on HG-induced podocytes injury. Also, miR-31-5p relieved HG-induced podocytes injury, and this effect also could be reversed by KLF9 overexpression. CONCLUSION: In summary, our data showed that hsa_circ_0037128 could promote HG-induced podocytes injury via regulating miR-31-5p/KLF9 axis, showing that hsa_circ_0037128 might be a target for DN treatment.

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

Effect of obstructive sleep apnea on glucose metabolism.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, ß-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS: OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS: These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.

Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound.

Infection is a major co-morbidity that contributes to impaired healing in diabetic wounds. Although impairments in diabetic neutrophils have been blamed for this co-morbidity, what causes these impairments and whether they can be overcome, remain largely unclear. Diabetic neutrophils, isolated from diabetic individuals, exhibit chemotaxis impairment but this peculiar functional impairment has been largely ignored because it appears to contradict the clinical findings which blame excessive neutrophil influx as a major impediment to healing in chronic diabetic ulcers. Here, we report that exposure to glucose in diabetic range results in impaired chemotaxis signaling through the formyl peptide receptor (FPR) in neutrophils, culminating in reduced chemotaxis and delayed neutrophil trafficking in the wound of Leprdb (db/db) type two diabetic mice, rendering diabetic wound vulnerable to infection. We further show that at least some auxiliary receptors remain functional under diabetic conditions and their engagement by the pro-inflammatory cytokine CCL3, overrides the requirement for FPR signaling and substantially improves infection control by jumpstarting the neutrophil trafficking toward infection, and stimulates healing in diabetic wound. We posit that CCL3 may have therapeutic potential for the treatment of diabetic foot ulcers if it is applied topically after the surgical debridement process which is intended to reset chronic ulcers into acute fresh wounds.

Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3ß/Nrf2 pathway.

Serine/threonine protein kinase 25 (STK25) has critical importance for diabetic complications. However, whether STK25 has a link with diabetic retinopathy is not clearly understood. The damages of retinal ganglion cells (RGCs) caused by high glucose (HG) is a critical determinant for the onset of diabetic retinopathy. Herein, this work focused on assessing the possible role of STK25 in HG-evoked damage to RGCs. An expression abundance of STK25 was occurred in RGCs challenged with HG. STK25 loss lowered the deleterious effects on RGCs, including apoptosis, oxidative stress and inflammation. SKT25 silencing strengthened the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in HG-challenged RGCs. Moreover, the inhibition of STK25 restored the phosphorylation of AKT and glycogen synthase kinase-3ß (GSK-3ß) in HG-challenged RGCs, whereas limiting AKT decreased the motivating effects of STK25 inhibition on the Nrf2 pathway. Additionally, the beneficial effects of STK25 inhibition on HG injuries were also reversed via the inhibition of Nrf2. Based on these observations, our work suggests that the inhibition of STK25 is protective for RGCs suffering HG injuries, which is achieved by effects on the AKT-GSK-3ß/Nrf2 pathway. STK25 may participate in the onset of diabetic retinopathy by affecting HG-evoked damages of RGCs.

Novel Motor-Sparing Ultrasound-Guided Neural Injection in Severe Carpal Tunnel Syndrome: A Comparison of Four Injectates.

Nerve hydrodissection uses fluid injection under pressure to selectively separate nerves from areas of suspected entrapment; this procedure is increasingly viewed as potentially useful in treating carpal tunnel syndrome (CTS). The usage of normal saline (NS), 5% dextrose water (D5W), platelet-rich plasma (PRP), and hyaluronic acid (HA) as primary injectates for hydrodissection without an anesthetic can limit anesthetic-related toxicity and preserve the motor functions of the median nerve. Here, we describe a novel motor-sparing neural injection and compare the effect of these four injectates for severe CTS. We retrospectively reviewed the outcomes of 61 severe CTS cases after a single neural injection with NS, D5W, PRP, or HA. Outcomes were evaluated on the 1st and 6th months postinjection, including the Boston Carpal Tunnel Questionnaire (BCTQ) scores and the nerve cross-sectional area (CSA). The results revealed that PRP, D5W, and HA were more efficient than NS at all measured time points (p < 0.05), except for CSA at the 1st month between the NS and D5W groups. Single-injections of PRP and D5W seemed more effective than that of HA within 6 months postinjection for symptom and functional improvement (6th-month BCTQ-symptom, D5W vs. HA, p = 0.047; 1st-month BCTQ-symptom, PRP vs. HA, p = 0.018; 1st- and 6th-month BCTQ-function, D5W vs. HA, p = 0.002 and 0.016, respectively; 1st-month BCTQ-function, PRP vs. HA, p < 0.001). For reducing CSA, PRP and HA seemed more effective than D5W (HA > PRP > D5W on the 1st month and HA vs. D5W, p = 0.001; PRP > HA > D5W on the 6th month and PRP vs. D5W, p = 0.012).

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial.

OBJECTIVE: We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B). RESEARCH DESIGN AND METHODS: In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime ("early dinner timing") and a late condition scheduled 1 h prior to habitual bedtime ("late dinner timing"), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. RESULTS: Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in ß-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018). CONCLUSIONS: Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.

The role of microRNA-155 in glomerular endothelial cell injury induced by high glucose.

OBJECTIVE: To investigate the role of microRNA-155-5p on apoptosis and inflammatory response in human renal glomerular endothelial cells (HRGEC) cultured with high glucose. METHODS: The primary HRGEC were mainly studied, light microscopy was used to detect changes in cell morphology. Quantitative Real Time-Polymerase Chain Reaction, Western Blot, immunofluorescence were aimed to observe the mRNA and protein expression levels of target gene ETS-1, downstream factors VCAM-1, MCP-1 and cleaved caspase-3 in each group after high glucose treatment as well as transfection with miR-155 mimics or inhibitor. RESULTS: The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose treatment. Compared with normal-glucose treatment, the expression of microRNA-155 markedly increased in HRGECs treated with high-glucose, as well as the mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3. Overexpression of microRNA-155 remarkably downregulated mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3, whereas miRNA-155 knockdown upregulated their levels. In addition, HRGEC cells were transfected with miR-155 mimics and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1. CONCLUSION: MiR-155 can negatively regulate the expression of target gene ETS-1 and its downstream factors VCAM-1, MCP-1 and cleaved caspase-3, thus mediating the inflammatory response and apoptosis of HRGEC.

Upregulation of TGF-ß type II receptor in high glucose-induced vascular smooth muscle cells.

BACKGROUND: Mortality in patients with diabetes mellitus is estimated above 65% due to cardiovascular diseases. The aim of study was to investigate the effects of high-glucose conditions on TGF-ß type II receptor (TGFBR2) expression levels, cell viability, and migration rate in vascular smooth muscle cells (VSMCs). METHODS: VSMCs were incubated in 30 mM and 50 mM of glucose for 24 h, 48 h, and 72 h periods. The gene and protein expression levels were investigated by Real-time qRT-PCR and western blotting techniques, respectively. The cell viability was evaluated by MTT assay. VSMC migration rate was also studied by wound healing assay. RESULTS: The TGFBR2 gene and protein expression levels were significantly upregulated in all the groups treated with glucose in 24 h, 48 h, and 72 h periods. The cell viability was not significantly affected in values of 30 mM and 50 mM of glucose. The increase of migration rate of VSMCs was not significant. CONCLUSION: The results suggested the increased expression levels of TGFBR2 in the response to high glucose conditions may modulate the cellular events through the signaling pathway network in VSMCs.

Rapid fluctuations in brain oxygenation during glucose-drinking behavior in trained rats.

Proper inflow of oxygen into brain tissue is essential for maintaining normal neural functions. Although oxygen levels in the brain's extracellular space depend upon a balance between its delivery from arterial blood and its metabolic consumption, the use of high-speed electrochemical detection revealed rapid increases in brain oxygen levels elicited by various salient sensory stimuli. These stimuli also increase intrabrain heat production, an index of metabolic neural activation, but these changes are slower and more prolonged than changes in oxygen levels. Therefore, under physiological conditions, the oxygen inflow into brain tissue exceeds its loss due to consumption, thus preventing any metabolic deficit. Here, we used oxygen sensors coupled with amperometry to examine the pattern of real-time oxygen fluctuations in the nucleus accumbens during glucose-drinking behavior in trained rats. Following the exposure to a glucose-containing cup, oxygen levels rapidly increased, peaked when the rat initiated drinking, and relatively decreased during consumption. Similar oxygen changes but more episodic drinking occurred when Stevia, a calorie-free sweet substance, was substituted for glucose. When water was substituted for glucose, rats tested the water but refused to consume all of it. Although the basic pattern of oxygen changes during this water test was similar to that with glucose drinking, the increases were larger. Finally, oxygen increases were significantly larger when rats were exposed to concealed glucose and made multiple unsuccessful attempts to obtain and consume it. Based on these data, we discuss the mechanisms underlying behavior-related brain oxygen fluctuations and their functional significance.NEW & NOTEWORTHY Oxygen sensors coupled with high-speed amperometry were used to examine brain oxygen fluctuations during glucose-drinking behavior in trained rats. Oxygen levels rapidly increased following presentation of a glucose-contained cup, peaking at the initiation of glucose drinking, and relatively decreasing during drinking. Oxygen increases were larger when rats were exposed to concealed glucose and made multiple attempts to obtain it. We discuss the mechanisms underlying behavior-related brain oxygen fluctuations and their functional significance.

A 5% Glucose Solution for the Liquid Formulation Gemcitabine Solvent Decreases Gemcitabine-induced Vascular Pain.

BACKGROUND/AIM: Gemcitabine (GEM)-induced vascular pain often occurs in patients. A 5% glucose solution for the lyophilized formulation of GEM solvent is known to decrease the frequency of GEM-induced vascular pain compared with saline. In this study, we aimed to examine the availability of glucose for a liquid formulation GEM solvent for the prevention of GEM-induced vascular pain. PATIENTS AND METHODS: In total, 214 patients with bile tract or pancreatic cancer, who received GEM-containing regimens, were enrolled in this retrospective study. The patients were divided into a glucose group, which was administered the liquid formation GEM diluted with glucose, and a saline group. The frequency of GEM-induced vascular pain was compared between them. RESULTS: Glucose significantly decreased the frequency of GEM-induced vascular pain during the first GEM administration (36% vs. 55%, p=0.005). CONCLUSION: Switching the solution for liquid formulation GEM from saline to glucose significantly decreased the frequency of vascular pain.