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At least 109 records · Page 6

Double contrast-enhanced ultrasound improves the detection and localization of occult lesions in the pancreatic tail: a initial experience report

Purpose: The aim of this study is to review our initial experience of Double contrast-enhanced ultrasonography (DCEUS) in the preoperative detection of pancreatic tail occult tumors. Methods: Thirty-five patients were recruited to undergo DCEUS of the pancreas suspected by occult lesions of pancreatic with MRI or clinical evidence. The radiologists assessed the images (conventional US, DCEUS, and MRI) for enhancement phases, tumor presence, location, enhancement characteristics, and tumor conspicuity. The differences in the onset times of the phases between DCEUS and MRI were noted. Tumor conspicuity was graded on a four-point scale for conspicuity comparison among three imaging modalities. Results: Pancreatic tail tumors were missed on conventional transabdominal US in 11 of 35 patients. DCEUS revealed 12 lesions of 35 patients. Pancreatic tail tumors were identified on MRI in 10 of 35 patients. The sensitivity and specificity of DCEUS for depicting occult lesions of ≤ 2.2 cm were 92% and 95%, respectively. In contrast, the sensitivity and specificity of conventional US were 67% and 66%, respectively. The sensitivity and specificity of MRI were 91% and 88%, respectively. The conspicuity ratings of the three phases did not significantly differ between the DCEUS and MRI groups (P > 0.05). The DCEUS phases started much earlier than the corresponding MRI phases. Conclusion: DCEUS is a promising technique in the detection of occult pancreatic tail tumors and is possibly superior to dynamic enhanced MRI in the case of some peripheral lesions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A case of human pancreatic eurytremiasis

This study provides the first comprehensive imaging report of human pancreatic eurytremiasis. A 43-year-old man with obstructive jaundice and a pancreatic tumor was referred for diagnosis and treatment. Serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase were elevated. Computed tomography (CT) revealed a multilocular cystic lesion with delayed enhanced area in the pancreas head. On magnetic resonance imaging, the tumor was hyperintense on diffusion-weighted image, and the apparent diffusion coefficient value of the tumor was lower than that of the normal pancreatic parenchyma. Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography ({sup 18}F-FDG PET/CT) revealed abnormally increased uptake of {sup 18}F-FDG in the tumor. A subtotal stomach-preserving pancreaticoduodenectomy was performed on the preoperative diagnosis of pancreatic carcinoma accompanied by branch duct-type intraductal papillary mucinous neoplasm. Multifocal granulomatous lesions with necrotic areas including many parasite eggs were seen on the histology. The final diagnosis was pancreatic eurytremiasis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Weight-adapted ultra-low-dose pancreatic perfusion CT: radiation dose, image quality, and perfusion parameters

Purpose: We evaluate the reliability and feasibility of weight-adapted ultra-low-dose pancreatic perfusion CT. Methods: A total of 100 (47 men, 53 women) patients were enrolled prospectively and were assigned to five groups (A, B, C, D, and E) with different combination of tube voltage and tube current according to their body weight. Radiation dose parameters including volume CT dose index (CTDI) and dose-length product (DLP) were recorded. Image quality was evaluated both subjectively and objectively (noise, signal-to-noise ratio, contrast-to-noise ratio). Perfusion parameters including blood flow (BF), blood volume (BV), and permeability (PMB) were measured. The dose, image quality measurements, and perfusion parameters were compared between the five groups using one-way analysis of variance (ANOVA). Results: Radiation dose reached 8.7 mSv in patients under 50 kg and was 18.9 mSv in patients above 80 kg. The mean subjective image quality score was above 4.45 on a 5-point scale with good agreement between two radiologists. Groups A–D had equivalent performance on objective image quality (P > 0.05), while Group E performed even better (P < 0.05). No significant differences emerged in comparison with perfusion parameters (BF, BV, PMB) of normal pancreas parenchyma between the five groups. Conclusion: Weight-adapted ultra-low-dose pancreatic perfusion CT can effectively reduce radiation dose without prejudice to image quality, and the perfusion parameters of normal parenchyma are accurate and reliable.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer

Characteristic features of chronic pancreatitis (CP) may be absent on standard imaging studies. Quantitative Magnetic Resonance Imaging (MRI) techniques such as T{sub 1} mapping, extracellular volume (ECV) fraction, diffusion-weighted imaging (DWI) with apparent diffusion coefficient map (ADC), MR elastography (MRE), and T{sub 1}-weighted signal intensity ratio (SIR) have shown promise for the diagnosis and grading severity of CP. However, radiologists still use the Cambridge classification which is based on traditional ductal imaging alone. There is an urgent need to develop new diagnostic criteria that incorporate both parenchymal and ductal features of CP seen by MRI/MRCP. Designed to fulfill this clinical need, we present the MINIMAP study, which was funded in September 2018 by the National Institutes of Health. This is a comprehensive quantitative MR imaging study which will be performed at multiple institutions in well-phenotyped CP patient cohorts. We hypothesize that quantitative MRI/MRCP features can serve as valuable non-invasive imaging biomarkers to detect and grade CP. We will evaluate the role of T{sub 1} relaxometry, ECV, T{sub 1}-weighted gradient echo SIR, MRE, arteriovenous enhancement ratio, ADC, pancreas volume/atrophy, pancreatic fat fraction, ductal features, and pancreatic exocrine output following secretin stimulation in the assessment of CP. We will attempt to generate a multi-parametric pancreatic tissue fibrosis (PTF) scoring system. We anticipate that a quantitative scoring system may serve as a biomarker of pancreatic fibrosis; hence this imaging technique can be used in clinical practice as well as clinical trials to evaluate the efficacy of agents which may slow the progression or reverse measures of CP.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

CT and MR imaging features of pancreatic adenosquamous carcinoma and their correlation with prognosis

Purpose: To retrospectively investigate the computed tomography (CT) and magnetic resonance (MR) imaging features of pancreatic adenosquamous carcinoma (PASC) and the association between imaging findings and prognosis. Materials and methods: CT, MR images of 26 patients with PASC were analyzed. Clinical symptoms, tumor markers, and patients’ survival were recorded. Tumor attenuation, enhancement pattern and degree, vessel involvement, adjacent tissue invasion and metastasis were evaluated. The association between imaging features and overall survival (OS) were also assessed using Cox proportional hazards ratio model. Results: Fourteen masses were found in the head of the pancreas and 12 in the body/tail. The mean tumor size was 4.47 ± 1.76 cm. PASC usually showed ill-defined (96.2%), lobulated (76.9%) and predominantly solid mass (92.3%). Ring enhancement in the peripheral area of the tumor was commonly seen (76.9%). Vessel invasion was seen in 17 cases (65.4%), encasement of adjacent arteries in 7 cases (26.9%), upstream main pancreatic duct (MPD) dilatation in 16 cases (61.5%) and double duct sign in 9 cases (34.6%). Multivariate Cox proportional hazards model demonstrated that patients with vessel invasion may predict a poor prognosis (p = 0.037). Conclusion: PASC tends to be an ill-defined solid mass with peripheral ring enhancement, and relatively poor enhancement in the central area. PASC may also show vessel invasion, vessel encasement and upstream MPD dilatation. Vessel invasion may indicate a poor prognosis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

MR-Guided High-Intensity Focused Ultrasound: Current Status of an Emerging Technology

The concept of ideal tumor surgery is to remove the neoplastic tissue without damaging adjacent normal structures. High-intensity focused ultrasound (HIFU) was developed in the 1940s as a viable thermal tissue ablation approach. In clinical practice, HIFU has been applied to treat a variety of solid benign and malignant lesions, including pancreas, liver, prostate, and breast carcinomas, soft tissue sarcomas, and uterine fibroids. More recently, magnetic resonance guidance has been applied for treatment monitoring during focused ultrasound procedures (magnetic resonance-guided focused ultrasound, MRgFUS). Intraoperative magnetic resonance imaging provides the best possible tumor extension and dynamic control of energy deposition using real-time magnetic resonance imaging thermometry. We introduce the fundamental principles and clinical indications of the MRgFUS technique; we also report different treatment options and personal outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Management of Respiratory Motion in Extracorporeal High-Intensity Focused Ultrasound Treatment in Upper Abdominal Organs: Current Status and Perspectives

Extracorporeal high-intensity focused ultrasound (HIFU) is a minimally invasive therapy considered with increased interest for the ablation of small tumors in deeply located organs while sparing surrounding critical tissues. A multitude of preclinical and clinical studies have showed the feasibility of the method; however, concurrently they showed several obstacles, among which the management of respiratory motion of abdominal organs is at the forefront. The aim of this review is to describe the different methods that have been proposed for managing respiratory motion and to identify their advantages and weaknesses. First, we specify the characteristics of respiratory motion for the liver, kidneys, and pancreas and the problems it causes during HIFU planning, treatment, and monitoring. Second, we make an inventory of the preclinical and clinical approaches used to overcome the problem of organ motion. Third, we analyze their respective benefits and drawbacks to identify the remaining physical, technological, and clinical challenges. We thereby consider the outlook of motion compensation techniques and those that would be the most suitable for clinical use, particularly under magnetic resonance thermometry monitoring.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Chemoembolization of Neuroendocrine Liver Metastases Using Streptozocin and Tris-acryl Microspheres: Embozar (EMBOsphere + ZAnosaR) Study

PurposeThe purpose of this prospective observational study was to evaluate the efficacy and tolerability of transarterial chemoembolization (TACE) for neuroendocrine liver metastases using a combination of streptozocin, Lipiodol, and tris-acryl microspheres.Patients and MethodsA total of 16 men and 9 women aged 59.6 ± 11.3 years, all with predominant liver disease, underwent 54 courses of TACE using an emulsion of 1.5 g of streptozocin and 10 ml of Lipiodol. Additional embolization was performed using 300–500 µm tris-acryl microspheres. Morphological response was evaluated using the RECIST criteria on multi-detector computed tomography or MRI. Clinical efficacy was evaluated particularly in patients with carcinoid syndrome.ResultsThe primary tumor was located in the small bowel or pancreas in 21 (84%) patients. Eleven (44%) patients presented with a carcinoid syndrome. Nineteen (76%) patients presented with more than 10 liver nodules. One delayed case of ischemic cholecystitis was treated conservatively. After a median follow-up of 36.1 months, 1 (4%) patient had a complete response, 12 (48%) patients had a partial response, and 7 (28%) patients had a stable disease corresponding to a disease control rate of 80%. All patients with carcinoid syndrome had significant improvement. Median time to progression was 18.8 months and overall survival was 100, 100, and 92% at 1, 2, and 3 years, respectively. Seven patients presented with extrahepatic progression with abdominal lymphadenopathies or metastases to the brain, ovary, adrenal gland, or lung.ConclusionOptimized TACE using a combination of streptozocin, Lipiodol, and tris-acryl microspheres is effective and well tolerated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Treatment of Visceral Transplant Pseudoaneurysms Using Physician-Modified Fenestrated Stent Grafts: Initial Experience

Pseudoaneurysms after visceral transplantation represent a significant risk to patients. We report the successful treatment of three transplant (pancreas, liver and kidney) artery anastomotic pseudoaneurysms using physician-modified fenestrated endovascular stent grafts. In all cases, surgical repair was considered high risk and would have compromised the arterial supply to the graft. The endovascular approach in all cases obviated the need for surgical intervention and maintained graft arterial supply.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Restoration of Dehiscent Pancreaticojejunostomy Causing a Major Postoperative Pancreatic Fistula by Reinsertion of a Pancreatic Duct Tube Using the Rendezvous Technique

Introduction: A postoperative clinically relevant pancreatic fistula can cause severe sequelae. We aimed to describe our minimally invasive procedure (rendezvous technique) for the treatment of a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence involving a dislodged main pancreatic duct tube. Methods: In our rendezvous technique, a guidewire is advanced into the jejunal lumen from the access site of the drainage tube and is caught by a snare catheter, which is used to replace the dislodged main pancreatic duct tube. Then, the guidewire is passed from the access site of the drainage tube to the site of the dislodged main pancreatic duct tube. A sheath is inserted along the route of the dislodged main pancreatic duct tube and is placed across the pancreaticojejunal anastomosis over the guidewire. Another guidewire is advanced into the main pancreatic duct via the sheath, and a new main pancreatic duct tube is inserted into the main pancreatic duct over the second wire. This technique was performed in two patients with a pancreatic fistula. Results: Our rendezvous technique was successfully performed in a 73-year-old man with an intractable clinically relevant pancreatic fistula and large discharge from the drain and a 74-year-old woman with a pancreatic fistula and fluid collection between the elevated jejunum and remnant pancreas. Discharge from the drain and fluid collection decreased after the procedure. Conclusion: Our rendezvous technique is an effective minimally invasive approach for a pancreatic fistula resulting from pancreaticojejunal anastomosis dehiscence.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Importance of m N{sup 6}-methyladenosine (m{sup 6}A) RNA modification in cancer

RNA methylation, which was identified back in 1970s, has gained remarkable interest in recent years as it was shown to be a reversible modification involved in many cellular processes like mRNA and miRNA processing, mRNA localisation, translation suppression, or activation. These, in turn, affect important bioprocesses such as tissue development, sex determination, and DNA damage response. Important group of proteins are responsible for adding, recognizing, and removing the methyl group to and from the RNA molecules, which are referred as writers, readers, and erasers, respectively. If any of the processes is not strictly controlled, this can cause abnormalities in gene expression, which result in diseases including cancers such as lung, pancreas, glioblastoma, and breast cancer. Mechanisms of RNA methylation and its role in various cancer types and diagnostic methods for RNA methylation are discussed in this article.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy

Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan–Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89–11.08) and 10.10 months (95% CI 6.30–12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

YY1 positively regulates human UBIAD1 expression

Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter.

60 APPLIED LIFE SCIENCES↗

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.

60 APPLIED LIFE SCIENCES↗

Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity

The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC{sub 50} 8–11 μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for intestines, liver, muscle and pancreas. In adipocytes, uptake inhibition was less effective (IC{sub 50} 58 μM). Inhibition was specific for long chain fatty acids and was ineffective toward medium chain fatty acids, which are transported by diffusion. Kinetic analysis of Grassofermata-dependent FA transport inhibition verified a non-competitive mechanism. By comparison with Grassofermata, several atypical antipsychotic drugs previously implicated as inhibitors of FA uptake were ineffectual. In mice Grassofermata decreased absorption of {sup 13}C-oleate demonstrating its potential as a therapeutic agent. - Highlights: • Grassofermata is a small compound inhibitor of FATP2. • Uptake inhibition is specific for long chain fatty acids. • Uptake kinetics shows low specificity for adipocytes compared to other cell types. • Inhibition is by a non-competitive mechanism. • Atypical antipsychotics do not inhibit FA uptake by comparison with Grassofermata.

60 APPLIED LIFE SCIENCES↗

Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic β-cells in obese type 2 diabetic db/db mice

It is well known that Sodium-Glucose Co-transporter 2 (SGLT2) inhibitors, new hypoglycemic agents, improve glycemic control by increasing urine glucose excretion, but it remained unclear how they exert protective effects on pancreatic β-cells. In this study, we examined the effects of SGLT2 inhibitor luseogliflozin on β-cell function and mass using obese type 2 diabetic db/db mice. Ten-week-old male diabetic db/db mice were treated with luseogliflozin 0.0025% or 0.01% in chow (Luse 0.0025% or Luse 0.01%) or vehicle (control) for 4 weeks. Urinary glucose excretion was increased in Luse groups (0.0025% and 0.01%) compared to control mice 3 days after the intervention. Fasting blood glucose levels were significantly lower in mice treated with Luse compared to control mice. Fasting serum insulin concentrations were significantly higher in mice treated with Luse compared to control mice. Triglyceride levels tended to be lower in Luse groups compared to control mice. In immunohistochemical study using pancreas tissues, β-cell mass was larger in Luse groups compared to control group which was due to the increase of β-cell proliferation and decrease of β-cell apoptosis. Furthermore, in gene analysis using isolated islets, insulin 1, insulin 2, MafA, PDX-1 and GLUT2 gene expression levels were significantly higher in Luse groups compared to control group. In contrast, expression levels of fibrosis-related gene such as TGFβ, fibronectin, collagen I and collagen III were significantly lower in Luse groups. In conclusion, SGLT2 inhibitor luseogliflozin ameliorates glycemic control and thus exerts protective effects on pancreatic β-cell mass and function. - Highlights: • SGLT2 inhibitor luseogliflozin ameliorates glycemic control in db/db mice. • Luseogliflozin increases β-cell proliferation and decreases β-cell apoptosis. • Luseogliflozin preserves various β-cell-specific gene expression. • Luseogliflozin decreases various fibrosis-related factors in db/db mice.

60 APPLIED LIFE SCIENCES↗

β-cell serotonin production is associated with female sex, old age, and diabetes-free condition

Serotonin is known to be present in pancreatic β-cells and to play several physiological roles, including insulin secretion, β-cell proliferation, and paracrine inhibition of α-cells. However, the serotonin production of different cell lines and islets has not been compared based on age, sex, and diabetes related conditions. Here, we directly compared the serotonin concentrations in βTC and MIN6 cell lines, as well as in islets from mice using ultra-performance liquid chromatography tandem mass spectrometry. The average serotonin concentration was 5–10 ng/mg protein in the islets of male and non-pregnant female mice. The serotonin level was higher in females than males at 8 weeks, although there was no difference at 1 year. Furthermore, we observed serotonin by immunofluorescence staining in the pancreatic tissues of mice and human. Serotonin was detected by immunofluorescence staining in a portion of β-cells from islets of old female mice, but not of male or young female mice. A similar pattern was observed in human pancreas as well. In humans, serotonin production in β-cells was associated with a diabetes-free condition. Thus, serotonin production in β-cells was associated with old age, female sex, and diabetes-free condition. - Highlights: • Actual serotonin concentrations in cell lines and islets are compared. • Serotonin over-production in mouse β-cell is aged and female specific. • Ovariectomy lowers serotonin concentrations in islets. • Serotonin over-production in human β-cell is aged, female, and non-diabetes specific.

60 APPLIED LIFE SCIENCES↗

Oral lipase activities and fat-taste receptors for fat-taste sensing in chickens

Highlights: • We cloned a fat-taste receptor candidate gene, CD36, from chickens. • Fat-taste receptor genes, GPR120 and CD36, were expressed in chicken oral tissues. • Several lipase genes were expressed in chicken oral tissues. • Chicken oral tissues contained functional lipases. It has been reported that a functional fat-taste receptor, GPR120, is present in chicken oral tissues, and that chickens can detect fat taste in a behavioral test. However, although triglycerides need to be digested to free fatty acids to be recognized by fat-taste receptors such as GPR120, it remains unknown whether lipase activities exist in chicken oral tissues. To examine this question, we first cloned another fat-taste receptor candidate gene, CD36, from the chicken palate. Then, using RT-PCR, we determined that GPR120 and CD36 were broadly expressed in chicken oral and gastrointestinal tissues. Also by RT-PCR, we confirmed that several lipase genes were expressed in both oral and gastrointestinal tissues. Finally, we analyzed the lipase activities of oral tissues by using a fluorogenic triglyceride analog as a lipase substrate. We found there are functional lipases in oral tissues as well as in the stomach and pancreas. These results suggested that chickens have a basic fat-taste reception system that incorporates a triglycerides/oral-lipases/free fatty acids/GPR120 axis and CD36 axis.

60 APPLIED LIFE SCIENCES↗