Histology Of Pancreas Research Articles

Pancreatic Injury Secondary to Renal Ischemia/Reperfusion (I/R) Injury: Possible Role of Oxidative Stress

Recent studies demonstrated remote effects of renal ischemia/reperfusion (I/R) injury on some organs such as brain, liver, and lungs. We investigated the effects of renal I-R injury on function, histology and oxidative stress state of pancreas. Twenty-four male adult Sprague-Dawley rats were divided equally into 2 groups; sham group: rats underwent midline laparotomy and dissection of renal pedicles without renal ischemia, and ischemic group: rats underwent bilateral renal ischemia for 45 min. Renal functions (serum creatinine and BUN), pancreatic functions (serum amylase, lipase and insulin) and fasting blood glucose were measured at 2 h, 1 day, 3 days and 7 days after ischemia. Also, pancreatic histology and malondialdehyde (MDA), catalase and reduced glutathione (GSH) were examined at 2 h and 7 days after ischemia. The ischemic rats showed significant increase in serum creatinine and BUN with significant increase in serum amylase and lipase at 2 h, 1 day and 3 days after ischemia. Blood glucose and fasting insulin showed no significant change apart from significant increase in insulin in sham group at 1 day after ischemia. Pancreas isolated from ischemic rats showed significant increase in histopathological damage score and significant increase in MDA and catalase enzyme with decrease in GSH. In conclusion, bilateral renal ischemia for 45 min caused significant impairment of pancreatic functions and histology. This might be due to deficiency of antioxidant and increased lipid peroxidations in pancreatic tissues.

Pharmacological characterization of different fractions of Calotropis procera (Asclepiadaceae) in streptozotocin induced experimental model of diabetic neuropathy

Ethnopharmacological relevanceCalotropis procera (Ait.) R.Br. is one of an ancient traditional shrub, which has been used for the treatment of diabetes, pain and inflammation for thousands of years in India. The root extract of Calotropis procera has been widely used by the tribal׳s of district Udaipur, Rajasthan (India) for treatment of diabetes mellitus and its associated complications like diabetic neuropathy. The present study was performed to explore the protective effect of root, stem and leaf extracts of Calotropis procera in diabetes and diabetic neuropathy against tactile allodynia, mechanical hyperalgesia and thermal hyperalgesia in streptozotocin induced diabetic rats. Materials and methodsDiabetes and peripheral neuropathy were induced in Wistar rats by injection of streptozotocin (45mg/kg/intraperitoneally). The roots, stem and leaves of Calotropis procera were sequentially extracted with petroleum ether, chloroform, ethyl acetate and methanol. All the extracts were assessed by oral administration at 100 and 250mg/kg in streptozotocin diabetic rats. The following compounds were used as positive controls: insulin NPH (1IU/kg/day), metformin (500mg/kg/day), glibenclamide (2.5mg/kg/day) and a combination of acarbose (20mg/kg/day) with methylcobalamine (500µg/kg/day). In contrast, the streptozotocin induced untreated diabetic rats termed as negative control. Thermal hyperalgesia, mechanical hyperalgesia and tactile allodynia were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy by Eddy׳s hot plate, tail immersion, Randall–Selitto and Von Frey hair tests. The basal nociceptive thresholds were assessed in week 4 of post streptozotocin injection. All groups received their treatment on a regular basis from 28 to 42 days following a confirmation of diabetic neuropathy. The nociceptive thresholds were assessed in all groups in week 5 and 6. The histopathology of pancreas and biochemical estimations of plasma insulin and glycosylated haemoglobin (HbA1C%) levels were also performed in week 6 of post streptozotocin injection. ResultsThe negative control rats developed diabetes and diabetic neuropathy after 6 week of streptozotocin administration distinguished by significant (p<0.01) hyperalgesia and tactile allodynia with enhanced HbA1C% level compared to normoglycemic rats. Chronic administration of root methanol, stem methanol and leaf ethyl-acetate extracts of Calotropis procera for 2 weeks at 100 and 250mg/kg doses significantly (p<0.01) attenuated the diabetes induced mechanical hyperalgesia, thermal hyperalgesia, tactile allodynia and HbA1C% level in streptozotocin diabetic rats as compared to negative control rats. Further, the root methanol extract of Calotropis procera in 100mg/kg dose showed the regeneration capability of β cells in the histology of pancreas with significant (p<0.01) improvement in plasma insulin level in streptozotocin diabetic rats compared to negative control rats. ConclusionRoot methanol extract of Calotropis procera (100mg/kg) has shown ameliorative effect in diabetic neuropathy which may be attributed by its multiple actions including potent hypoglycemic and antioxidant.

Effects of Parathyroid Hormone on Bone Mass, Bone Strength, and Bone Regeneration in Male Rats With Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM. Subcritical femoral defects were created in diabetic fa/fa and nondiabetic +/+ Zucker Diabetic Fatty (ZDF) rats and internally stabilized. Vehicle or 75 μg/kg/d PTH(1-84) was sc administered over 12 weeks. Skeletal effects were evaluated by μCT, biomechanical testing, histomorphometry, and biochemical markers, and defect regeneration was analyzed by μCT. Glucose homeostasis was assessed using glucose tolerance testing and pancreas histology. In diabetic rats, bone mass was significantly lower in the distal femur and vertebrae, respectively, and increased after PTH treatment by up to 23% in nondiabetic and up to 18% in diabetic rats (P < .0001). Diabetic rats showed 23% lower ultimate strength at the spine (P < .0005), which was increased by PTH by 36% in normal and by 16% in diabetic rats (P < .05). PTH increased the bone formation rate by 3-fold in normal and by 2-fold in diabetic rats and improved defect regeneration in normal and diabetic rats (P < .01). PTH did not affect serum levels of undercarboxylated osteocalcin, glucose tolerance, and islet morphology. PTH partially reversed the adverse skeletal effects of T2DM on bone mass, bone strength, and bone defect repair in rats but did not affect energy metabolism. The positive skeletal effects were generally more pronounced in normal compared with diabetic rats.

Comparative Effects of Low- and High-Glycemic Index Diets on Biochemical Variables and Organ Histology in Alloxanized Diabetic Rats

This experimentally-controlled designed study compared the effects of low -and highglycemic index diets on biochemical variables and organ histology in alloxan -induced diabetic rats (DR). Effects of low-GI (fried yam)and high-GI (roasted) diets on organ and body weights, pancreas histology, glycemic tolerance (GT) and lipid profile (LP) were determined and compared in the adult alloxan -induced (150mg/kg intraperitoneally) diabetic rats of 3 groups (8 ratseach) fed with standard rat feed (control), fried and roasted yam diets respectively for six weeks. Lipid profile and glycemic tolerance were analysed and determined using a dry-chemical automatic analyzer and oral D

Vanadyl sulfate treatment stimulates proliferation and regeneration of beta cells in pancreatic islets.

We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4 at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4 also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4 treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats.

Linoleic and alpha linolenic acids ameliorate streptozotocin-induced diabetes in mice

Streptozotocin (STZ)-induced diabetes in mice progresses with decreased desaturase activities and alterations in the metabolism of essential fatty acids (EFA). Objectives: Based on our previous studies with soybean oil that ameliorated the STZ damage in mice, we tested here the accountability of its main EFA components, i.e. linoleic acid (LA) and alpha linolenic acid (ALA), in the prevention of pancreas damage and Δ6 desaturase decrease. Materials and methods: Seven days after injection with STZ and EFA gavage, ICR mice were sacrificed. Plasma glucose and insulin levels, pancreas histology and liver fatty acid desaturases were analysed. Results: EFA reduced pancreas damage, insulin and glucose plasma levels and restored Δ6 desaturase activity and mRNA expression levels. Discussion: By reducing pancreas damage, EFA ameliorated insulin levels, Δ6 desaturase and fatty acid metabolism. LA further enhanced Fads2 promoter activity. Conclusion: EFA ameliorate STZ induced diabetes in mice.

Comparative Analysis of Pancreatic Changes in Aged Rats Fed Life Long With Sunflower, Fish, or Olive Oils

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. We aimed to study the effect of oil consumption on pancreas histology in order to find aging-related signs. To this end, three groups of rats were fed an isocaloric diet for 2 years, where virgin olive, sunflower, or fish oil was included. Pancreatic samples for microscopy and blood samples were collected at the moment of sacrifice. As a result, the sunflower oil-fed rats presented higher β-cell numbers and twice the insulin content than virgin olive oil-fed animals. In addition, rats fed with fish oil developed acinar fibrosis and macrophage infiltrates in peri-insular regions, compared with counterparts fed with virgin olive oil. Inflammation signs were less prominent in the sunflower group. The obtained data emphasize the importance of dietary fatty acids in determining pancreatic structure.

Taking Care of Pancreatitis, Not So Simple: IgG4-related Multiorgan Disease Presenting as Pancreatitis

Introduction: Autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related sclerosing disease. In type 1 AIP, extrapancreatic organs may be involved synchronously or metachronously. One hallmark of type 1 AIP is elevated serum IgG4 level. We report a patient presenting with pancreatitis found to have multiorgan involvement with IgG4-related disease in the setting of normal serum IgG4. Case: A 59-year-old male was seen in the gastroenterology clinic for complaint of abdominal pain for 4-5 months, worse with meals, associated with nausea, night sweats, and 20-pound weight loss in 3 months. He denied vomiting, diarrhea, hematemesis, melena, hematochezia. He quit smoking 3 years ago, alcohol 10 years ago. Past history: skin vasculitis treated with oral steroids 3 years ago. Two CT scan abdomen/pelvis in the last 4 months were unremarkable. Physical exam: tenderness in epigastrium, right upper quadrant. Laboratory value: lipase 1,322, amylase 384, BUN/creat 25/1.7, HB 12.2, alk phos 298, ESR >140, C-reactive protein 87.3, serum triglyceride 151. The patient was not on medication known to cause pancreatitis. He was treated with IV fluids, bowel rest, pain medication. MRI abdomen: diffuse pancreatic body enlargement, bilateral renal enlargement and enhancement. Further work up revealed ANA titer 1:80, positive rheumatoid factor, rest of autoimmune panel was negative. Total IgG 3359, IgM 79, IgA 183, IgE 40. IgG subclass levels were: IgG1 1,420, IgG2 953, IgG3 182, IgG4 40. At this point, considering multiorgan involvement with elevated total IgG, a kidney biopsy was obtained to confirm IgG4-related disease. Biopsy revealed lymphoplasmacytic infiltrate involving tubules with plasma cell staining for IgG4. Patient was started on oral prednisone with symptomatic improvement. Discussion: The prevalence of type 1 AIP is 2-11% in patients with chronic pancreatitis. International consensus diagnostic criteria for AIP involves five features: imaging of pancreatic parenchyma and duct, serology, other organ involvement, histology of pancreas, response to steroid therapy. The number of IgG4+ plasma cells is more sensitive and specific than serum IgG4. Not all patients with type I AIP exhibit elevated serum IgG4 levels as demonstrated in our patient.Figure: MRI: abnormal foci of ill-defined signal and enhancement in both kidneys, and pancreas.

Effects of intravenous administration of pentoxifylline in pancreatic ischaemia–reperfusion injury

BackgroundTherapeutic strategies to reduce the occurrence of pancreatic ischaemia–reperfusion (I–R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti‐inflammatory effect by inhibiting NF‐κB activation. This group has previously demonstrated that pentoxifylline induces an anti‐inflammatory response in acute pancreatitis and liver I–R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I–R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I–R injury. MethodsPancreatic I–R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I–R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and IL‐10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed. ResultsSignificant reductions in serum TNF‐α, IL‐6 and IL‐10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline‐treated animals, denoting less severe pancreatic histologic damage. ConclusionsPentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I–R injury and may be a useful tool in pancreas and kidney transplantation.

Efficacy of Evolvulus alsinoides (L.) L. on insulin and antioxidants activity in pancreas of streptozotocin induced diabetic rats.

AimDiabetes mellitus (DM), a leading non communicable disease with multiple etiologies is considered as third greatest cause of death in all over the world. During DM, persistent hyperglycemia causes an increased production of free radicals via auto oxidation of glucose and non-enzymatic protein glycation which may lead to disruption of cellular functions and oxidative damage to membranes. The present study was designed to investigate the therapeutic effect of Evolvulus alsinoides on antioxidant activity in pancreas of experimental diabetes.MethodsThe antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10% formalin for 24 hrs then the samples were stained with haemotoxylin-eosin for the microscopic observation.ResultsOral administration of plant extract for 45 days resulted in significant antioxidant activity, increases the insulin level and also inhibits lipid peroxidation in pancreas of streptozotocin induced diabetic rats. The histopathological studies showed the normal histology of pancreas after treatment with plant extract and glibenclamide. This study showed that the administration of Evolvulus alsinoides to streptozotocin induced diabetic rats improves the antioxidant activity and remodel the structure of pancreas due to the presence of secondary metabolites like phenols, flavonoids, alkaloids, steroids, terpenoids and glycosides in the ethanolic extract of plant material.ConclusionFrom the present study, it can be concluded that the plant extract effectively reduced the oxidative stress induced by streptozotocin and potentially increased the insulin level. Hence, it can be used in the management of diabetes mellitus.Electronic supplementary materialThe online version of this article (doi:10.1186/2251-6581-12-39) contains supplementary material, which is available to authorized users.

Effects of Aflatoxins on Performance and Exocrine Pancreas of Broiler Chickens

The aim of this research was to evaluate, on a weekly basis, the effects of aflatoxins on the activity of digestive enzymes (alpha-amylase, lipase, and trypsin) in the pancreas as well as on the performance and histology of pancreas in broiler chickens over the course of 42 days. One thousand and eighty 1-day-old male Cobb broilers were divided into four treatments with 18 replicates and 15 birds per replicate (i.e., 270 broilers per treatment). Treatments were established according to the amount of aflatoxins added to the diet, as follows: T1 = 0 mg of aflatoxins per kilogram of feed (mg/kg); T2 = 0.7 mg/kg; T3 = 1.7 mg/kg; and T4 = 2.8 mg/kg. Pancreas sample collection was performed from one bird out of each replicate at 7, 14, 21, 28, 35, and 42 days of experiment, which yielded a total of 18 samples per treatment on each collection. Each sample was homogenized in distilled water, frozen in liquid nitrogen, lyophilized, and stored at -20 C until analysis. Performance parameters (body weight, feed consumption, and feed conversion rate) were measured at 21, 35, and 42 days of experiment. At the end of the experiment (42 days), six birds from each treatment were randomly chosen for histologic evaluation of the pancreas. The presence of aflatoxins in the diet induced a negative effect on all performance parameters. The pancreatic activity of lipase and alpha-amylase were significantly increased in treatments T3 and T4, while the specific activity of trypsin was only affected during treatment T4. In addition, several histologic changes were observed in the pancreas of birds receiving aflatoxin-contaminated feed. Aflatoxins present in the feed determined an increase in the activity of pancreatic enzymes in broilers, affecting the digestibility of the diet, thereby leading to losses in performance and productivity.

PWE-058 Tissue Acquisition from Solid Pancreatic Lesions – Endoscopy or Surgery

IntroductionThe accurate diagnosis of solid pancreatic masses is important in directing appropriate management of patients. The methods commonly used are percutaneous, laparoscopic and EUS guided biopsy of these lesions. Laparoscopic...

Histologic Effects of University of Wisconsin Two-Layer Method Preservation of Rat Pancreas

Marginal donors represent a poorly utilized source of organs for transplantation despite their availability. The key is to reduce the ischemic damage in the effort to improve organ quality. This study investigated the histologic effects after in situ perfusion of preservation with a two-layer method compared with the classic University of Wisconsin preservation in term of tissue integrity and number of viable exocrine cells in the rat pancreas both after exsanguination and at 8 weeks of cryopreservation. Pancreata harvested from 60 rats were collected using 3 methods: two-layer method following University of Wisconsin perfusion; exsanguination; and classic University of Wisconsin perfusion/storage. In addition to histologic analysis of collected pancreata, we analyzed the number of CK19+ cells and their viability using chi-square tests with values P < .05 considered to be significant. Rat pancreas histology showed as University of Wisconsin in situ perfusion and preservation by the two-layer method to be more effective to maintain the morphologic integrity of both exocrine and endocrine tissues. There were a larger number of CK19+ cells with good viability. Moreover, the effects of oxygenation were visible in pancreas biopsies preserved after exsanguination. In situ University of Wisconsin perfusion and preservation for 240 minutes with the two-layer method yielded greater numbers and viability of CK19+ cells even after 8 weeks of cryopreservation.

Overexpressed miRNA-155 dysregulates intestinal epithelial apical junctional complex in severe acute pancreatitis

To investigate whether miRNA-155 (miR-155) dysregulates apical junctional complex (AJC) protein expression in experimental severe acute pancreatitis (SAP). Twenty-four male BALB/c mice were randomly assigned to two groups: the SAP group (n = 12) receiving sequential intraperitoneal injection of 50 µg/kg caerulein and 10 mg/kg lipopolysaccharide over 6 h, and the control group (n = 12) receiving intraperitoneal injection of normal saline. Animals were sacrificed 3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens. Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage. Levels of serum amylase, diamine oxidase (DAO), and tumor necrosis factor (TNF)-α were determined using commercial kits. Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA. miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction. Target genes for miR-155 were predicted using the miRTarBase database, RNA22 and PicTar computational methods. Western blotting was performed to quantitate the protein expression levels of the target gene RhoA, as well as zonula occludens (ZO)-1 and E-cadherin, two AJC component proteins. Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage (SAP vs control, 10.0 ± 2.0 vs 3.2 ± 1.2, P < 0.01) and intestinal epithelial barrier damage (3.2 ± 0.7 vs 1.4 ± 0.7, P < 0.01). Levels of serum amylase (21.6 ± 5.1 U/mL vs 14.3 ± 4.2 U/mL, P < 0.01), DAO (21.4 ± 4.1 mg/mL vs 2.6 ± 0.8 mg/mL, P < 0.01), and TNF-α (61.0 ± 15.1 ng/mL vs 42.9 ± 13.9 ng/mL, P < 0.01) increased significantly in SAP mice compared to those in control mice. miR-155 was significantly overexpressed in SAP intestinal epithelia (1.94 ± 0.50 fold vs 1.03 ± 0.23 fold, P < 0.01), and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155. RhoA (22.7 ± 5.8 folds vs 59.6 ± 11.6 folds, P < 0.01), ZO-1 (46 ± 18 folds vs 68 ± 19 folds, P < 0.01), and E-cadherin proteins (48 ± 15 folds vs 77 ± 18 folds, P < 0.01) were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP (0.97 ± 0.18 folds vs 1.01 ± 0.17 folds, P > 0.05). TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1, and E-cadherin by downregulating post-transcriptional RhoA expression, and disrupts intestinal epithelial barrier in experimental SAP.

FTY720 preserved islet β‐cell mass by inhibiting apoptosis and increasing survival of β‐cells in db/db mice

FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by β-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in β-cells in db/db mice treated with FTY720 16 weeks. Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses. FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored β-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved β-cell mass by inhibiting apoptosis and increasing β-cell survival in pancreatic islets. We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving β-cell mass by inhibiting apoptosis and increasing survival of islet β-cells.

Hipoglicemia hiperinsulinêmica da infância: Análise de dados clínicos de uma amostra brasileira

To review the presentation of hyperinsulinemic hypoglycemia of the infancy (HHI), its treatment and histology in Brazilian pediatric endocrinology sections. The protocol analyzed data of birth, laboratory results, treatment, surgery, and pancreas histology. Twenty-five cases of HHI from six centers were analyzed: 15 male, 3/25 born by vaginal delivery. The average age at diagnosis was 10.3 days. Glucose and insulin levels in the critical sample showed an average of 24.7 mg/dL and 26.3 UI/dL. Intravenous infusion of the glucose was greater than 10 mg/kg/min in all cases (M:19,1). Diazoxide was used in 15/25 of the cases, octreotide in 10, glucocorticoid in 8, growth hormone in 3, nifedipine in 2 and glucagon in 1. Ten of the cases underwent pancreatectomy and histology results showed the diffuse form of disease. This is the first critic review of a Brazilian sample with congenital HHI.

Amelioration of hyperglycemia, hyperlipidemia, oxidative stress and inflammation in steptozotocin-induced diabetic rats fed a high fat diet by riceberry supplement

Dark purple riceberry bran contains a higher dietary fiber and antioxidant compounds than unpigmented rice bran. Riceberry supplement (RB) was used to evaluate the effects on biochemical parameters, skeletal muscle glucose transporter 4 (GLUT4), oxidative stress and inflammation in a streptozotocin (STZ)-induced diabetes rat. To elucidate the effects were due to dietary fiber supplementation and/or bioactive components, equivalent amounts of dietary fiber present in RB were also fed to STZ-induced diabetic rats. Diabetes Sprague–Dawley rats (non-FBG⩾16.65mM) were randomly divided into five groups: DM fed a high fat (HF) diet, DM-RB1 fed 5% RB, DM-RB2 fed 41% RB, DM-F1 fed 0.6% fiber and DM-F2 fed 5% fiber. After 12weeks, significant improvement of BG, insulin, HbA1C, IPGTT and GLUT4 levels were observed in DM-RB1 and DM-RB2 groups. Hyperlipidemia was significantly improved in DM-RB2 and DM-F2 groups. Oxidative stress (TBARS), antioxidant enzymes (SOD, CAT, and GPx), antioxidant capacity (ORAC), pro-inflammation cytokine (TNF-α and IL-6) were improved in DM-RB1 and DM-RB2 groups. Improvement of pancreas and spleen histology was found in DM-RB1 and DM-RB2 groups. These indicate the potential of RB to improve hyperglycemia and hyperlipidemia conditions as well as alleviate oxidative stress and inflammation.

Tocotrienol Rich Fraction Prevents Fenitrothion Induced Pancreatic Damage by Restoring Antioxidant Status

Fenitrothion (FNT) is extensively used as pesticide and may induce oxidative stress in various organs. Tocotrienol, a form of vitamin E found in palm oil, reduces oxidative impairments in pathological conditions. This study aims to investigate the effects of palm oil tocotrienol rich fraction (TRF) on fenitrothion-induced oxidative damage in rat pancreas. Forty male Sprague-Dawley rats were divided into four groups: control group, FNT group, TRF group and FNT+TRF group. Regimens FNT (20 mg kg(-1) b.wt.) and TRF (200 mg kg(-1) b.wt.) were force-fed for 28 consecutive days with control group only receiving corn oil. Chronic administration of fenitrothion significantly (p < 0.05) induced oxidative damage in pancreas of rats with elevated malondialdehyde and protein carbonyl level. Depletion of glutathione and significant (p < 0.05) reduction in antioxidant enzyme activities in pancreas homogenate additionally suggested induction of oxidative stress. Despite these changes in pancreas of intoxicated rats, no significant (p < 0.05) changes in blood glucose and pancreas histology were observed. Co-administration of FNT with TRF alleviated these oxidative changes and significantly (p < 0.05) restored antioxidant status. Enzymatic activities of Superoxide Dismutase (SOD) and Catalase (CAT) were normalized. In conclusion, tocotrienol rich fraction of palm oil prevents fenitrothion-induced pancreatic oxidative damage in rats.

Effect of double-balloon enteroscopy on pancreas: an experimental porcine model.

To evaluate the effect of double-balloon enteroscopy (DBE) on pancreas histology and levels of pancreatic enzymes. Conventional upper gastrointestinal endoscopy was performed on five control pigs. Oral DBE was performed with an EN-450T5 enteroscope on 20 pigs. Two experimental groups (10 pigs each) were defined according to DBE duration: 90 min for Group 1 and 140 min for group 2. During oral insertion, the balloons were not inflated in the descending part of the duodenum to avoid the minor duodenal papilla. Serum amylase, lipase and C-reactive protein (CRP) levels were monitored before the procedure and repeated every 30 min until the exploration was finished, as well as 24 h and 7 d after. After the procedure and for a total of 7 d, the pigs were observed twice a day for signs of decreased activity, irritability, vomiting or anorexia. Gross and microscopic examination of the pancreas was performed on day 7. All animals tolerated DBE without clinical manifestations of acute pancreatitis. Experimental groups had higher levels of enzymes than the control group at 24 h. Throughout the exploration, the amylase levels increased significantly above the baseline 24 h after DBE, although the increase was not statistically significant and did not reach 20% of the baseline. An increase in lipase and CRP was observed at 24 h after the procedure, although by day 7, all enzymatic levels had returned to baseline. No differences between groups 1 and 2 were found for any enzyme and sampling site during and after the procedure. Similarly, no correlation between insertion depth and enzyme levels was observed. Direct in situ and post-removal inspection of the pancreas did not show any evidence of fluid collection, abscesses or hemorrhage. Histological examination of the pancreas from groups 1 and 2 revealed the existence of focal areas (0.14-0.26 mm2) of ischemic necrosis in 47.4% of the animals. In the pigs with damaged pancreas, the left lobe (tail) was always affected. However, this only happened in 83.3% of the samples from the right lobe (head) and in 33.3% of the samples from the body of the pancreas. Significant differences were found between the left lobe (tail) and the body for the percentage of affected pancreas. Both the size of the lesions and the percentage of affected pancreas were higher in the left pancreatic lobe (tail). The presence of the lesions was not related to the exploration length. The increase in pancreatic enzymes after DBE could be related to focal points of pancreatic ischemic necrosis due to mechanical stress.

Effects of Liraglutide on β-Cell-Specific Glucokinase-Deficient Neonatal Mice

The glucagon-like peptide-1 receptor agonist liraglutide is used to treat diabetes. A hallmark of liraglutide is the glucose-dependent facilitation of insulin secretion from pancreatic β-cells. In β-cells, the glycolytic enzyme glucokinase plays a pivotal role as a glucose sensor. However, the role of glucokinase in the glucose-dependent action of liraglutide remains unknown. We first examined the effects of liraglutide on glucokinase haploinsufficient (Gck(+/-)) mice. Single administration of liraglutide significantly improved glucose tolerance in Gck(+/-) mice without increase of insulin secretion. We also assessed the effects of liraglutide on the survival rates, metabolic parameters, and histology of liver or pancreas of β-cell-specific glucokinase-deficient (Gck(-/-)) newborn mice. Liraglutide reduced the blood glucose levels in Gck(-/-) neonates but failed to prolong survival, and all the mice died within 1 wk. Furthermore, liraglutide did not improve glucose-induced insulin secretion in isolated islets from Gck(-/-) neonates. Liraglutide initially prevented increases in alanine aminotransferase, free fatty acids, and triglycerides in Gck(-/-) neonates but not at 4 d after birth. Liraglutide transiently prevented liver steatosis, with reduced triglyceride contents and elevated glycogen contents in Gck(-/-) neonate livers at 2 d after birth. Liraglutide also protected against reductions in β-cells in Gck(-/-) neonates at 4 d after birth. Taken together, β-cell glucokinase appears to be essential for liraglutide-mediated insulin secretion, but liraglutide may improve glycemic control, steatosis, and β-cell death in a glucokinase-independent fashion.