Morphology Of Pancreas Research Articles

Multiparametric quantitative MRI of healthy adult pancreas: correlations with gender and age

BackgroundThe pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored.PurposeTo establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age.Materials and methodsThe T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated.ResultsThe T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10−3 mm2/s, respectively. T2 values were significantly different between genders (P < 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P < 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, −0.45, and −0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years.ConclusionThis study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease.

Impact of heparanase-2 (Hpa2) on cancer and inflammation: Advances and paradigms.

HPSE2, the gene-encoding heparanase 2 (Hpa2), is mutated in urofacial syndrome (UFS), a rare autosomal recessive congenital disease attributed to peripheral neuropathy. Hpa2 lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase (Hpa1), yet it exhibits a high affinity toward HS, thereby inhibiting Hpa1 enzymatic activity. Hpa2 regulates selected genes that promote normal differentiation, tissue homeostasis, and endoplasmic reticulum (ER) stress, resulting in antitumor, antiangiogenic, and anti-inflammatory effects. Importantly, stress conditions induce the expression of Hpa2, thus establishing a feedback loop, where Hpa2 enhances ER stress which, in turn, induces Hpa2 expression. In most cases, cancer patients who retain high levels of Hpa2 survive longer than patients bearing Hpa2-low tumors. Experimentally, overexpression of Hpa2 attenuates the growth of tumor xenografts, whereas Hpa2 gene silencing results in aggressive tumors. Studies applying conditional Hpa2 knockout (cHpa2-KO) mice revealed an essential involvement of Hpa2 contributed by the host in protecting against cancer and inflammation. This was best reflected by the distorted morphology of the Hpa2-null pancreas, including massive infiltration of immune cells, acinar to adipocyte trans-differentiation, and acinar to ductal metaplasia. Moreover, orthotopic inoculation of pancreatic ductal adenocarcinoma (PDAC) cells into the pancreas of Hpa2-null vs. wild-type mice yielded tumors that were by far more aggressive. Likewise, intravenous inoculation of cancer cells into cHpa2-KO mice resulted in a dramatically increased lung colonization reflecting the involvement of Hpa2 in restricting the formation of a premetastatic niche. Elucidating Hpa2 structure-activity-relationships is expected to support the development of Hpa2-based therapies against cancer and inflammation.

Differential effects of fish-oil and cocoa-butter based high-fat/high-sucrose diets on endocrine pancreas morphology and function in mice.

A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice. C57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells. Fish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas β-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function.

Aspartame and diet soda impact on blood sugar and insulin in Wistar rat

Research reports on the safety of Aspartame as a sugar substitute which was intended to reduce the prevalence of metabolic disorders has been inconclusive. Thus, this study is aimed at investigating the effects of aspartame and diet soda on body weight, blood sugar and insulin levels. Thirty seven Wistar rats were divided into: Group 1 (5): control group and administered 5ml of distilled water daily. Groups 2 and 3 (8 each) received high and low doses of diet soda respectively. Groups 4 and 5 (8 each) received high (45 mg/ kg b.w) and low (22.5 mg/kg b.w) doses of aspartame respectively. After 10 weeks, the rats were subjected to an overnight fast for the determination of fasting blood sugar test after which they were sacrificed. Blood samples were collected and the pancreas harvested and put in formal saline for histological analysis. Insulin level was measured using ELISA technique. Results show various morphological changes in the pancreas of all experimental groups, including hypoplastic islet, vascular congestion and ulceration, nerve hypertrophy, amongst others. Body weight was significantly increased in groups given high diet soda (114 ± 0.12g) and aspartame (121 ± 0.17g) when compared with the control (85 ± 0.21g). However, there was no significant difference in fasting blood sugar and insulin levels in all treated groups compared to control. In conclusion, this study has shown that chronic consumption of aspartame and diet soda increased body weight, but no effect on blood sugar and insulin levels. The adverse effects on pancreas morphology suggest impending health implications.

Comparative Study on the Gross Anatomy of Some Abdominal Organs in Albino Rat (Rattus norvegicus) and Albino Mouse (Mus musculus)

A comparative gross anatomical study was carried out on six apparently healthy adult male albino rats (Rattus norvegicus) and albino mice (Mus musculus) (Three rats and three mice) The aim of the current work is to demonstrate the gross anatomical topography, morphology and fixation of (liver, kidney, spleen, stomach and pancreas) in order to highlight similarities and differences between both species. The animals were brought from local animal markets and delivered to the anatomy laboratory of the Faculty of Veterinary Medicine Cairo University, Egypt. After euthanasia, animals were anatomically dissected via mid laparotomy to study the concerned abdominal viscera in both species. The organs were removed separately and preserved by both freezing and immersion in a container filled with 10% neutral buffered formalin solution for further examination. Photographs of the organs insitu and isolated were taken, discussed and compared with that of the other lab mammals in previous literatures. The study confirmed the absence of the gall bladder and the round ligament of liver in albino rat, while the hepatorenal ligament was absent in albino mouse. Also, the site of renal impression was found to be located on the right lateral hepatic lobe in albino rat while on the caudate process of liver in the albino mouse. Albino rats and mice had a bean shaped smooth unipapillated kidneys, however the position of kidneys greatly varied between both species. The characteristic crescentic-shaped stomach in rats with a tightly closed esophageal opening compared to the thumb-shaped stomach of mice with slightly loose esophageal opening were anatomical remarks. The proper knowledge of the normal morphology and topography of these abdominal viscera would assist veterinarians in designing of therapeutic surgical approaches in abdominal cavity and experimental transplantations.

Photobiomodulation in diabetic rats: effects on morphological, pancreatic parameters and glucose homeostasis.

Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by STZ (60 mg/Kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.

294-LB: Altered a-Cell Phenotype in Pancreata Is Associated with Increased Peri-islet Collagen Ceposition

Cystic fibrosis (CF)-related diabetes (CFRD) affects up to 50% of adults with CF, adding to treatment burden and impacting overall wellbeing. Major changes are observed in pancreas morphology with acinar tissue replaced by fibrosis and/or fat. Islets are still present even in advanced disease and may cluster together. It is believed CFRD is caused by impaired insulin secretion and loss of β-cell mass, however, detailed pathogenesis remains unknown. We investigated post-mortem pancreatic tissue from 19 donors with CF (age range: premature-27 years) and 10 donors without CF (6-65 years). CF pattern of injury (fibrotic/lipoatrophic) was assessed by routine histology. Sirius Red/Fast Green stain was used to assess fibrosis. Artificial intelligence analysis was performed to quantify intra-islet and peri-islet collagen distribution in 16 cases (7 CF, 9 control). Triple immunofluorescence staining for insulin, glucagon, and vimentin followed by confocal microscopy was used to image up to 50 islets per donor. Glucagon and vimentin-positive (glu/vim+) α-cells were observed in both CF and non-CF pancreata (mean (range) 32 (0-90)% of islets). The presence of this altered α-cell phenotype positively correlated with age in all donors (R=0.41, p<0.05). Presence of glu/vim+ α-cells correlated with peri-islet collagen density in analysed CF and control cases (glu/vim+ islets 44 (0-82)%) (R=0.60, p<0.05). In control pancreata alone glu/vim+ cells were seen in 1-82% (mean 41%) islets and correlated positively with intra-islet collagen density (R=0.76, p<0.05). Interestingly, two CF cases with confirmed diabetes showed low prevalence of this altered phenotype (2% of islets) with 13 vs 40% fibrosis in the whole section. Our data provide further evidence for exocrine-endocrine signalling in the human pancreas and suggest that presence of vimentin-expressing α-cells may be driven by increased collagen deposition in the islet microenvironment during aging and in CFRD pathogenesis. Disclosure N. Kattner: None. S. Richardson: None. Y. Al-selwi: None. D. Tiniakos: None. J. A. Shaw: Advisory Panel; Betalin Therapeutics, Provention Bio, Inc., Consultant; Mogrify. Funding Cystic Fibrosis Trust (SRC019)

1757-P: δ-α Cell-to-Cell Interaction Modulates Pancreatic Islet Ca2+ Oscillation Modes

Glucose-stimulated pancreatic islets show α cell mass dependent fast and slow Ca2+ oscillations. It implicates structure-function relationship is a fundamental principle of pancreatic islets. Despite the low percentage within the islet, the δ cells entangle with α cells and occupy the islet periphery, to envelop the β cells in the core. However, the contribution of the extensive δ-α paracrine organization to the origin of the variability in Ca2+ activation, remains unclear. Here we found that somatostatin’s perturbation on Ca2+ oscillation critically depended on α cell mass. Furthermore, pharmacological and opto-geneticalperturbation on δ-α cell interaction cause islets to repeatably show fast and slow Ca2+ oscillations. Our study highlights the importance of δ-α cell interactions as the origin of the variability in oscillation pattern. Studying islets in their intact pancreas morphology in tissue slice revealed that glucose recruited the δ cells to control the α and β cell activity. Disclosure H.Ren: None.

Pancreas and islet morphology in cystic fibrosis: clues to the etiology of cystic fibrosis-related diabetes.

Cystic fibrosis (CF) is a multi-organ disease caused by loss-of-function mutations in CFTR (which encodes the CF transmembrane conductance regulator ion channel). Cystic fibrosis related diabetes (CFRD) occurs in 40-50% of adults with CF and is associated with significantly increased morbidity and mortality. CFRD arises from insufficient insulin release from β cells in the pancreatic islet, but the mechanisms underlying the loss of β cell function remain understudied. Widespread pathological changes in the CF pancreas provide clues to these mechanisms. The exocrine pancreas is the epicenter of pancreas pathology in CF, with ductal pathology being the initiating event. Loss of CFTR function results in ductal plugging and subsequent obliteration. This in turn leads to destruction of acinar cells, fibrosis and fatty replacement. Despite this adverse environment, islets remain relatively well preserved. However, islet composition and arrangement are abnormal, including a modest decrease in β cells and an increase in α, δ and γ cell abundance. The small amount of available data suggest that substantial loss of pancreatic/islet microvasculature, autonomic nerve fibers and intra-islet macrophages occur. Conversely, T-cell infiltration is increased and, in CFRD, islet amyloid deposition is a frequent occurrence. Together, these pathological changes clearly demonstrate that CF is a disease of the pancreas/islet microenvironment. Any or all of these changes are likely to have a dramatic effect on the β cell, which relies on positive signals from all of these neighboring cell types for its normal function and survival. A thorough characterization of the CF pancreas microenvironment is needed to develop better therapies to treat, and ultimately prevent CFRD.

Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model.

Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.

108-OR: The Effect of Human Pregnancy on Morphology of the Endocrine Pancreas

In animal models, pregnancy is associated with distinct morphological and functional adaptations in the endocrine pancreas, particularly characterized by β cell hyperplasia and hypertrophy. Failed islet adaptation to increased metabolic demands in pregnancy contributes to the development of gestational diabetes. However, the effects of pregnancy on the remodeling of human endocrine pancreas remain largely unknown. To address this, we used human pancreatic autopsy specimens from 8 women who died during pregnancy or within 6 weeks postpartum (P/PP) , and 16 women who were matched by age and body mass index (BMI) to serve as controls (CON) who were not pregnant at death. Subjects had a complete autopsy with pancreatic tissue of adequate quality/quantity stored and a corresponding medical record. Consecutive pancreatic sections were co-immunostained for key islet cell markers including Insulin, Glucagon and Glucagon-Like Peptide-1 (GLP-1) as well as a marker of cell proliferation (Ki-67) . Although the pancreatic fractional insulin area (β cell area) was comparable between P/PP and CON groups, the glucagon and the GLP-1 positive areas were substantially increased ∼2-fold in the P/PP group (p<0.05) . Our analysis also revealed an increase in the proportion of GLP-1/glucagon double positive islet cells (p<0.05) in PP/P subjects, suggesting a modulatory effect of pregnancy in favor of increased islet GLP-1 production in α cells. Consistently, P/PP subjects demonstrated an increase in α cell expression of prohormone convertase 1/3 (PC1/3) (p<0.05) , an enzyme responsible for the proteolytic cleavage of GLP-1 from proglucagon. Finally, the frequency of both β and α cell proliferation was comparable between groups (p>0.05) . While prior pre-clinical studies have focused solely on functional and morphological changes in pancreatic β cells, our data suggest that proglucagon gene products (glucagon and GLP-1) may play an underappreciated role in (or serve as markers of) the metabolic changes impacting human pregnancy. Disclosure A.M.Egan: None. T.K.Her: None. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.Matveyenko: None. Funding National Institutes of Health (K12 HD065987/HD/NICHD)

Towards developing a robust radiomics signature in diffuse diseases of the pancreas: Accuracy and stability of features derived from T1-weighted magnetic resonance imaging

BackgroundRadiomics of the pancreas has the potential to personalize the management of patients with diseases that are characterized by diffuse involvement of the pancreas. However, to date, radiomics features that are both clinically useful and reproducible have not been reported. MethodsIndividuals with definite chronic pancreatitis and healthy individuals, matched on sex and age, were prospectively recruited and underwent T1-weighted magnetic resonance imaging of the pancreas at 3T. A total of 107 radiomics features (shape, first-order texture, and second-order texture) were extracted using PyRadiomics and compared between the two groups, taking into account false discovery rate. Stability of significant texture features was investigated by subjecting magnetic resonance images of the pancreas to two core non-overlapping image pre-processing methods – intensity normalization and intensity discretisation. ResultsThirty-one (28.9%) radiomics features were significantly different between the two groups. These included 6 shape features, 6 first-order texture features, and 19 second-order texture features. ‘Kurtosis’ was significantly different between the two groups after both intensity normalization and intensity discretisation. ‘Total energy’, ‘energy’, ‘mean’, ‘root mean squared’, ‘10th percentile’, and ‘GLCM correlation’ were significantly different between the two groups after intensity discretisation. ConclusionThe identified radiomics features that are both accurate in characterizing definite diffuse changes in the pancreas morphology and stable irrespective of computational settings (and, therefore, reproducible) are positioned well to form the basis for development of a robust radiomics signature in diffuse diseases of the pancreas.

Synergistic hypoglycemic and hypolipidemic effects of ω-3 and ω-6 fatty acids from Indian flax and sesame seed oils in streptozotocin-induced diabetic rats

• The ω-3 and ω-6 FAs (ALA and LA) rich oils from FSO an SSO respectively, mitigated the diabetes induced by streptozotocin. • The In vitro and In vivo studies have revealed that the combination of FSO+SSO significantly increased the antioxidant enzymes like CAT, SOD, GSH, and decreased MDA levels in the pancreas and liver of streptozotocin induced rats. • The reduction was observed in the lipid profiles of TG, TC, LDL, VLDL, and increase in HDL, and also significant reduction in the hematological parameters such as AST, ALT, ALP, creatinine, urea, HbA1c and decreased blood glucose levels, while, TP, Hb and insulin levels were markedly increased in the treated rats in a dose-dependent manner compared to the diabetic control. • The results were also confirmed by histopathological examinations. • Combination of FSO+SSO shown more synergistic hypoglycemic, hypolipidemic and antioxidant potential compared to their individual treatments. Omega-3 and 6 fatty acids (FAs) of flaxseed oil (FSO) and sesame seed oil (SSO) that are being used in traditional foods and medicine have been investigated for their various synergistic biological potencies. However, their synergistic antidiabetic and antilipidemic properties at the world health organization (WHO) recommended ratio have not been studied. To evaluate the synergistic antidiabetic and antipidemic potentials of bioactive-fatty acids from flaxseed (FS) and sesame seeds (SS) against streptozotocin (STZ)-induced diabetes mellitus Wistar albino rats. The study was to determine the in vitro and in vivo synergistic antidiabetic and antipidemic potentials of ω-3 and ω-6 FAs at 1:5 ratio from FSO and SSO in STZ-induced diabetes mellitus rats. Fifty-four Wistar albino rats were divided into 9 groups: normal control; diabetic control received streptozotocin 45 mg/kg b.w IP; diabetic groups received standard drug tolbutamide orally received 5mg/kg b.w; FSO and SSO orally administered with 250 and 350; 516 and 700 mg/kg b.w PO respectively, and FSO+SSO at 43+292 and 86+584 mg/kg b.w PO respectively. Blood glucose levels were observed on weekly basis. At the end of the experiment, biochemical factors such as the level of antioxidant enzymes, serum liver enzymes, malondialdehyde level, lipid profiles, blood parameters, and pancreas morphology were studied. Twenty-eight days of the treatment significantly increased the in vivo antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), whereas, malondialdehyde (MDA) level was markedly decreased in a dose-dependent manner in the pancreas and liver. A noteworthy reduction was observed in the lipid profiles of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and increase in high-density lipoprotein (HDL), and also significant reduction was observed in the hematological parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, urea, glycosylated hemoglobin (HbA1c) and decreased blood glucose levels, while, total protein (TP), hemoglobin (Hb) and insulin levels were markedly increased in the treated rats in a dose-dependent manner compared to the diabetic control. Additionally, the results were also confirmed by histopathological examinations. The study suggested that the ω-3 and ω-6 FAs from FSO and SSO, respectively, showed potential synergistic antidiabetic and antilipidemic effects that were mainly mediated by ω-3 and ω-6 FAs present in the respective seed oils. Synergistic hypoglycemic and hypolipidemic effects of ω-3 and ω-6 fatty acids from Indian flax and sesame seed oils in Streptozotocin-induced diabetic rats

Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis.

BACKGROUNDThe expression of amino acid transporters is known to vary during acute pancreatitis (AP) except for LAT1 (slc7a5), the expression of which remains stable. LAT1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin (mTOR) activity, a phenomenon often observed in cancer cells. The mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet known.AIMTo evaluate the role of LAT1 in the development of and recovery from AP.METHODSAP was induced with caerulein (cae) injections in female and male mice expressing LAT1 or after its knockout (LAT1 Cre/LoxP). The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight, assessing microscopical tissue architecture, mRNA and protein expression, protein synthesis, and enzyme activity levels, as well as by testing the recruitment of immune cells by FACS and ELISA.RESULTSThe initial injury, evaluated by measurements of plasma amylase, lipase, and trypsin activity, as well as the gene expression of dedifferentiation markers, did not differ between the groups. However, early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout mice. Especially in females, we observed less mTOR reactivation and dysfunctional autophagy. The later regeneration phase was clearly delayed in female LAT1 knockout mice, which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein (rbpjl) and basic helix-loop-helix family member A15 (mist1). Amylase mRNA and protein levels remained lower, and, strikingly, female LAT1 knockout mice presented signs of fibrosis lasting until day seven. In contrast, pancreas morphology had returned to normal in wild-type littermates.CONCLUSIONLAT1 supports the regeneration of acinar cells after AP. Female mice lacking LAT1 exhibited more pronounced alterations than male mice, indicating a sexual dimorphism of amino acid metabolism.

Counter effects of Vitamin E against Outcomes of Alcohol Toxicity in Pancreatic Acini: Histomorphometric Study

Aim: To evaluate the effects of alcohol on the microscopic morphology of the exocrine pancreas and blood serum amylase and to explored that if vitamin E has a protective role against alcohol-induced damage in the pancreas of rabbits. Study design: Analytical experimental study Place and duration of study: Departments of Anatomy, Pathology and Pharmacology in Peshawar Medical College Pakistan from 1st January 2019 to 30th June 2019. Methodology: Eighteen healthy adult male domestic rabbits weighing 1-1.5 kg were chosen (oryctolaguscuniculus). The control group A received proper food and normal saline as drinking water, experimental group B received proper diet and 30 percent ethanol solution (30ml/kg/day) orally daily with normal saline, and experimental group C received proper diet, 30 percent ethanol solution (30ml/kg/day), vitamin E (50mg/kg/day) orally daily with normal saline. Each rabbit's blood was taken for serum amylase. Morphology of acinar cells included: 1) number of cells, (10 acini/field, 2) size of acini, 3) size of acinar cells, and 4) size of acinar nuclei. Results: Normal value of serum amylase in rabbits was found. The difference in serum amylase levels between the control and experimental groups for both E4 and E8 animals was not statistically significant. There was no significant difference in the number of pancreatic acinar cells, size of pancreatic acini, the pancreatic acinar cell size, and pancreatic acinar cells nuclear size in the control and experimental groups for both E4 and E8 animals. Conclusion: Alcohol consumption had no influence on the histomorphology of the rabbits' pancreatic acini in a short period (4-8 weeks). No significant variation was noted in the pancreatic acinar cells count & size, pancreatic acinar cells nuclear count and size, and pancreatic acini size. Therefore, protective role of vitamin E was not usefully identified. Keywords: Alcohol, Pancreas, Histomorphology, Vitamin E, Serum amylase

Combination therapy of Allium cepa L. and Cucumis sativa L. extracts in streptozotocin-induced diabetic rat model

BackgroundThe study assessed the effects of aqueous extracts of Allium cepa, Cucumis sativa and their combined formulation (1:1) on changes in body weight, fasting blood glucose level (FBGL), pancreas morphology and serum lipid concentration in streptozotocin-induced diabetic rats. Forty-two male rats were randomly assigned to six groups: A, B, C, D, E, and F (n = 7). Except for the control animals (group A), diabetes mellitus was experimentally induced in other groups (B to F) via a single intraperitoneal injection of freshly prepared streptozotocin. Thereafter, the diabetic control animals (group B) were left untreated and other diabetic groups were treated as follows: C (Allium cepa 10 mL/kg of body weight (mL/kg BW), D (Cucumis sativa 10 mL/kg BW), E (Allium cepa and Cucumis sativa 10 mL/kg BW), and F (Metformin 12 mg/kg BW). All treatments lasted for seven days and FBGL was monitored at two days intervals. The rats were then sacrificed, and blood samples were collected for serum lipid estimation.ResultsTreatments of diabetic rats with Allium cepa, Cucumis sativa and their combined formulation prevented significant (P < 0.05) loss in body weight which was evident in the diabetic control counterparts. Similarly, the various treatment options curtailed the hike in blood glucose induced by streptozotocin. The hypoglycemic effect of Allium cepa was particularly notable and comparable to that of Metformin. Serum high-density lipoprotein and low-density lipoprotein-cholesterols which were significantly altered in the diabetic control animals were restored to near normal following treatments with Cucumis sativa, and its combination with Allium cepa. These observations were substantiated by the outcome of the histopathological examination of the representative pancreases.ConclusionAllium cepa appears to be more effective in blood glucose homeostasis in the diabetic animals compared to Cucumis sativa and their combined formulation. Conversely, Cucumis sativa and its combination with Allium cepa had better effects on the physiological levels of serum cholesterols in the animals. Regular consumption of Allium cepa and Cucumis sativa may be helpful in controlling blood glucose and cholesterol levels in the diabetics.

Defining type 2 diabetes remission: KISS goodbye to confusion?

The concept that type 2 diabetes can revert to glycaemic levels below the diabetes threshold without diabetes medications (type 2 diabetes remission) is increasingly appreciated. Metabolic surgery results in a substantial proportion of people having type 2 diabetes remission, although the proportion reduces over time. 1 Sjostrom L Peltonen M Jacobson P et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014; 311: 2297-2304 Crossref PubMed Scopus (628) Google Scholar Randomised clinical trials incorporating a low energy total diet replacement phase have shown that, with maintained weight loss of at least 10 kg, type 2 diabetes remission is possible in a significant proportion of people. 2 Lean MEJ Leslie WS Barnes AC et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019; 7: 344-355 Summary Full Text Full Text PDF PubMed Scopus (258) Google Scholar , 3 Taheri S Zaghloul H Chagoury O et al. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 2020; 8: 477-489 Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar In one trial, 3 Taheri S Zaghloul H Chagoury O et al. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 2020; 8: 477-489 Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar which included younger patients (aged 18–50 years) with short duration of diabetes, 43 (61%) of 70 participants had type 2 diabetes remission at 12 months (defined as HbA1c <6·5% [48 mmol/mol] for ≥3 months). Substantial weight loss is associated with reduced liver and pancreatic fat, and with restoration of pancreatic morphology and β-cell insulin secretory capacity. 4 Al-Mrabeh A Hollingsworth KG Shaw JAM et al. 2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2020; 8: 939-948 Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 5 Taylor R Al-Mrabeh A Sattar N Understanding the mechanisms of reversal of type 2 diabetes. Lancet Diabetes Endocrinol. 2019; 7: 726-736 Summary Full Text Full Text PDF PubMed Scopus (80) Google Scholar Carbohydrate restriction can also result in glycaemic levels below the diabetes threshold through a combination of weight loss and reduced carbohydrate intake. 6 Brown A McArdle P Taplin J et al. Dietary strategies for remission of type 2 diabetes: a narrative review. J Hum Nutr Diet. 2021; (published online July 29.)https://doi.org/10.1111/jhn.12938 Crossref Scopus (3) Google Scholar Younger age, early-stage disease, lower number of diabetes medications, and greater weight loss are indicators for type 2 diabetes remission for both surgical and non-surgical interventions. The greatest challenge to sustaining type 2 diabetes remission is maintenance of weight loss and lifestyle change.

Syngeneic bone marrow transplantation in combination with PI3K inhibitor reversed hyperglycemia in later-stage streptozotocin-induced diabetes.

BackgroundType 1 diabetes (T1D) is a multiple factor autoimmune disease characterized by T cell-mediated immune destruction of islet β cells. Autologous hematopoietic stem cell transplantation (AHSCT) has been a novel strategy for patients with new-onset T1D, but not for those with a later diagnosis. Disturbance of regulatory T cells (Tregs) likely contributes to poor response after transplantation in later-stage T1D. Inhibition of phosphoinositide 3-kinases (PI3K)/Akt signaling maintains Tregs’ homeostasis.MethodsWe built a later-stage streptozotocin (STZ)-induced T1D mouse model. Syngeneic bone marrow transplantation (syn-BMT) was performed 20 days after the onset of diabetes in combination with BKM120 (a PI3K inhibitor). Meanwhile, another group of STZ-diabetic mice were transplanted with bone marrow cells cocultured with BKM120 in vitro for 24 h. Fasting glucose and glucose tolerance were recorded during the entire experimental observation after syn-BMT. Samples were collected 126 days after syn-BMT. Hematoxylin and eosin (H&E) staining was used to detect the effect of PI3K inhibitor combined with syn-BMT on morphology of the T1D pancreas. CD4+CD25− T cells and CD4+CD25+ T cells were sorted by magnetic cell sorting (MACS), then fluorescence activated cell sorting (FACS) and quantitative real-time PCR (qPCR) were used to detect the effect of PI3K inhibitor on modulating immune disorder and restoring the function of Treg cells.ResultsOur investigation showed syn-BMT in combination with BKM120 effectively maintained normoglycemia in later-stage T1D. The disease remission effects may be induced by the rebalance of Th17/Tregs dysregulation and restoration of Tregs’ immunosuppressive function by BKM120 after syn-BMT.ConclusionsThese results may reveal important connections for PI3K/Akt inhibition and Tregs’ homeostasis in T1D after transplantation. AHSCT combining immunoregulatory strategies such as PI3K inhibition may be a promising therapeutic approach in later-stage T1D.

A combination of melatonin and moderate-intensity aerobic exercise improves pancreatic beta-cell function and glycemic homeostasis in type 2 diabetic model of animals

Nocturnal melatonin secretion is important for preservation of ß-cell mass and function. Knowing that type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia caused by the elevated resistance of peripheral tissues to insulin, reduction in pineal melatonin and disturbances of insulin secretion by pancreatic ß-cells. In this context, exercise is considered one of the most valuable non-pharmacological approaches for treatment of T2DM. Considering the beneficial role of melatonin on glycemic metabolism in physical exercise, we investigated the effects of moderate-intensity aerobic exercise plus melatonin on glycemic homeostasis, the morphology and architecture of pancreas in spontaneous T2DM animals [Goto-Kakizaki (GK) rats]. The results confirmed that melatonin alone reduced the mass of epididymal white adipose tissue (WAT); however, only the combination of melatonin and physical exercise significantly reduced caloric intake, body weight, WAT and improved glucose tolerance and insulin sensitivity in T2DM rats. This combination also reduced apoptosis of cells in pancreatic islets. We observed either melatonin or the combination was able to reduce insulinemia. However, only the combination improved the morphology of the pancreatic islets. Thus, we conclude that in GK rats, melatonin plays a crucial role in the functionality of the pancreas to improve insulin sensitivity of peripheral tissues and, consequently, to maintain the glucose homeostasis. In addition, the combination is more efficiency to improve glucose tolerance and integrity of pancreatic islets in GK rats than melatonin alone.

A prospective study of prognostic factors predicting outcome of surgery in chronic pancreatitis at a tertiary care centre in India

Identification of factors predicting the outcome of surgery for chronic pancreatitis and preparation of a scoring system to predict the outcome following surgery. A total number of 76 patients who had undergone surgery for chronic pancreatitis were prospectively followed at Department of General Surgery, S.C.B. Medical College, Cuttack during the period from 2010-2013. Data on demographic details, pain score, opioid addiction, exocrine and endocrine insufficiency, insulin requirement and morphology of pancreas on imaging were recorded. On follow up, improvement in pain score and exocrine and endocrine insufficiency were recorded. Factors affecting surgical outcome were determined and a scoring system was done. The mean age of patients was 39.7±7.9 years (range 18-58 years). Chronic alcohol intake was the predominant cause accounting for 56% (n=34) cases. Mean pain score at admission on Visual Analogue Scale (VAS) was 5.98. Twenty-six patients (43.3%) were found to have endocrine insufficiency and 22 (36.6%) patients had exocrine insufficiency. Forty-two patients underwent Partington-Rochelle procedure, and 18 patients underwent Frey’s procedure. Eighty percent of patients (n=48) had significant pain relief. On logistic regression, preoperative VAS score, number of previous admissions, opioid dependence, main pancreatic duct (MPD) diameter, number and site of calcifications were found to be significant in predicting pain relief. Cohort of patients with chronic pancreatitis likely to get benefit from surgery can be predicted preoperatively.