Pancreatic Crosstalk in the Disease Setting: Understanding the Impact of Exocrine Disease on Endocrine Function.

The exocrine and endocrine are functionally distinct compartments of the pancreas that have traditionally been studied as separate entities. However, studies of embryonic development, adult physiology, and disease pathogenesis suggest there may be critical communication between exocrine and endocrine cells. In fact, the incidence of the endocrine disease diabetes secondary to exocrine disease/dysfunction ranges from 25% to 80%, depending on the type and severity of the exocrine pathology. Therefore, it is necessary to investigate how exocrine-endocrine "crosstalk" may impact pancreatic function. In this article, we discuss common exocrine diseases, including cystic fibrosis, acute, hereditary, and chronic pancreatitis, and the impact of these exocrine diseases on endocrine function. Additionally, we review how obesity and fatty pancreas influence exocrine function and the impact on cellular communication between the exocrine and endocrine compartments. Interestingly, in all pathologies, there is evidence that signals from the exocrine disease contribute to endocrine dysfunction and the progression to diabetes. Continued research efforts to identify the mechanisms that underlie the crosstalk between various cell types in the pancreas are critical to understanding normal pancreatic physiology as well as disease states. © 2024 American Physiological Society. Compr Physiol 14:5371-5387, 2024.

High circulating fibroblast growth factor-21 levels as a screening marker in fatty pancreas patients.

Background: The study aimed to detect the serum levels of fibroblast growth factor-21 (FGF-21) in fatty pancreas (FP) patients and to investigate their potential clinical value. Methods: We screened patients with FP using transabdominal ultrasound. The anthropometric, biochemical and serum levels of FGF-21 were compared between the FP group and the normal control (NC) group. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum FGF-21 for FP patients. Results: Compared with the NC group, body mass index, fasting blood glucose levels, uric acid levels and cholesterol levels of the FP group were significantly higher, while the high-density lipoprotein level was lower. In addition, levels of serum FGF-21, resistin, leptin and tumor necrosis factor-α were significantly higher than those in the NC group, while the serum adiponectin level was lower. Pearson analysis showed serum FGF-21 levels in FP patients were negatively correlated with leptin. The ROC curve showed the best critical value of the serum FGF-21 level in FP patients was 171 pg/mL (AUC 0.744, P = 0.002, 95% confidence intervals 0.636-0.852). Conclusion: Serum FGF-21 was closely related to fatty pancreas. Detecting serum FGF-21 levels may help identify the population susceptible to FP.

Fic-mediated AMPylation tempers the unfolded protein response during physiological stress.

The proper balance of synthesis, folding, modification, and degradation of proteins, also known as protein homeostasis, is vital to cellular health and function. The unfolded protein response (UPR) is activated when the mechanisms maintaining protein homeostasis in the endoplasmic reticulum become overwhelmed. However, prolonged or strong UPR responses can result in elevated inflammation and cellular damage. Previously, we discovered that the enzyme filamentation induced by cyclic-AMP (Fic) can modulate the UPR response via posttranslational modification of binding immunoglobulin protein (BiP) by AMPylation during homeostasis and deAMPylation during stress. Loss of fic in Drosophila leads to vision defects and altered UPR activation in the fly eye. To investigate the importance of Fic-mediated AMPylation in a mammalian system, we generated a conditional null allele of Fic in mice and characterized the effect of Fic loss on the exocrine pancreas. Compared to controls, Fic-/- mice exhibit elevated serum markers for pancreatic dysfunction and display enhanced UPR signaling in the exocrine pancreas in response to physiological and pharmacological stress. In addition, both fic-/- flies and Fic-/- mice show reduced capacity to recover from damage by stress that triggers the UPR. These findings show that Fic-mediated AMPylation acts as a molecular rheostat that is required to temper the UPR response in the mammalian pancreas during physiological stress. Based on these findings, we propose that repeated physiological stress in differentiated tissues requires this rheostat for tissue resilience and continued function over the lifetime of an animal.

Fundamentos que caracteriza la adherencia a la insulinoterapia de los pacientes con diabetes tipo II / Foundations that characterize adherence to the insulin therapy of patients with type II diabetes

La diabetes Mellitus es un padecimiento que empieza cuando el páncreas no realiza un uso adecuado de la insulina que produce o no puede lograr producir insulina. Se descomponen en glucosa en la sangre todos los alimentos ricos en hidratos de carbono; la insulina da ayuda a la glucosa para que esta pueda ingresar en las células. Los niveles de azúcar en la sangre al no funcionar bien el páncreas suben, lo cual debe ser controlado por medio de un tratamiento médico de por vida, y lo más importante la persona debe cambiar de hábitos en su salud. Objetivo: El objetivo principal de esta investigación es definir el efecto que produce la adherencia a la insulinoterapia en los pacientes con diabetes tipo II del Hospital del Día Mariana de Jesús. Materiales y Métodos: Se utilizó una investigación cuantitativa, transversal ya que se realizó una encuesta a los pacientes, la cual se procedió a la recolección y análisis e interpretación de datos. La muestra trabajada fue de 100 pacientes, los cuales fueron atendidos en el Hospital por concepto de diabetes tipo II en el área de emergencia. Resultados: Como resultado de la investigación tenemos que el 76% de los encuestados conocen sobre el tratamiento de la insulinoterapia, el 85% se rehusó a utilizar insulina cuando inició su tratamiento, el 75% ha tenido dificultad para la conservación de la insulina, el 63% considera que el uso de la insulina es riesgos, el 53% indicó haber recibido asesoría sobre los posibles efectos de la insulina, al 65% de encuestados su jornada laboral no le permite asistir a su control médico, el 72% ha sentido un desmejoro en su salud al dejar el tratamiento y el 63% de los encuestados indicó que ha abandonado en algún momento su tratamiento por temor a los efectos secundarios que dicen tener. Conclusiones: Se estableció el tipo de complicaciones que se dan en los pacientes ante la no adherencia a la insulinoterapia, uno de ellos fue, que al dejar el tratamiento los pacientes sintieron un desmejoro en su estado de salud, así también, los pacientes han abandonado el tratamiento en algún momento por miedo a los efectos secundarios que dicen tener la insulina(AU)

Diabetes Mellitus is a condition that begins when the pancreas does not make proper use of the insulin it produces or cannot achieve produce insulin. All foods rich in glucose are broken down into glucose in the blood. carbohydrates; insulin helps glucose to enter the cells cells. When the pancreas does not work well, blood sugar levels rise, which must be controlled by lifelong medical treatment, and most importantly the person must change their health habits. Objective: The main objective of this research is to define the effect produced by adherence to insulin therapy in patients with type II diabetes at Hospital del Día Mariana de Jesús. Materials and Methods: A quantitative, cross-sectional investigation was used since a patient survey which proceeded to the collection and analysis and interpretation of data. The sample worked was 100 patients who were treated at the Hospital for type II diabetes concept in the emergency area. Results: Like result of the investigation we have that 76% of the respondents know about the insulin therapy treatment, 85% refused to use insulin when they started their treatment, 75% have had difficulty conserving insulin, 63% considers that the use of insulin is risky, 53% indicated having received counseling about the possible effects of insulin, 65% of those surveyed did not care about their working hours. allows them to attend their medical control, 72% have felt a deterioration in their health when leaving the treatment and 63% of those surveyed indicated that they had abandoned their treatment at some point. treatment for fear of the side effects they claim to have. Conclusions: If established the type of complications that occur in patients due to non-adherence to insulin therapy, one of them was that when leaving the treatment the patients felt a deterioration in their state of health, as well as the patients have abandoned the treatment at some point for fear of the side effects that they claim to have insulin(AU)

Larger Volume and Higher Fat Content of the Pancreatic Head Are Predictive Factors for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVES: Acute pancreatitis is the most critical complication of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we investigated the association between the volume/fat content of the pancreatic head and the incidence of post-ERCP pancreatitis (PEP). METHODS: We retrospectively enrolled 157 patients who underwent ERCP. The volume and fat content of the pancreas were calculated by multislice computed tomographic imaging by using a volume analyzer. Multivariate analysis was performed to identify risk factors for PEP. RESULTS: The mean volumes of the whole pancreas and pancreatic head were significantly larger, and the fat content of the pancreatic head was significantly higher in the PEP group (P < 0.01). There were no significant differences in the mean volume and fat content of the pancreatic body and tail in the PEP group. Multivariate analysis revealed that the pancreatic guidewire placement (odds ratio [OR], 12.4; P < 0.01), pancreatic head volume (OR, 5.3; P < 0.01), and the pancreatic head fat content (OR, 4.8; P < 0.01) were independent risk factors for PEP. CONCLUSIONS: The pancreatic head volume and fat content were independent predicting factors of PEP. Quantitative assessment of the pancreas may contribute to the prediction of PEP onset.

Diallyl Disulfide Attenuates STAT3 and NF-κB Pathway Through PPAR-γ Activation in Cerulein-Induced Acute Pancreatitis and Associated Lung Injury in Mice.

We have previously shown that diallyl disulfide (DADS) protects mice against cerulein-induced acute pancreatitis (AP) and associated lung injury. However, the molecular mechanisms underlying its effect and the components involved have not been studied. We hypothesized that DADS may reduce TNF-α, CSE expression, H2S production, STAT3, and NF-κB activation and induce SOCS3 expression through peroxisome proliferator-activated receptor γ (PPAR-γ) pathway in cerulein-induced mice. Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50 µg/kg) for 6 h. Diallyl disulfide (200 µg/kg) was administered in the presence or absence of PPAR-γ antagonist GW9662 (0.3 mg/kg) (i.p) 1 h after the induction of AP. Our findings revealed that DADS blocked TNF-α, CSE expression, H2S production, and STAT3, and NF-κB activation was reversed by GW9662. Furthermore, GW9662 abrogated DADS-induced SOCS3 expression. The results show for the first that DADS-induced anti-inflammatory effect in acute pancreatitis is regulated through PPAR-γ.

Rationale for and Development of the Pancreatic Quantitative Sensory Testing Consortium to Study Pain in Chronic Pancreatitis.

OBJECTIVES: Abdominal pain is the primary symptom of chronic pancreatitis (CP), but pain is difficult to assess, and objective methods for pain assessment are lacking. The characterization of the sensory component of pain as a surrogate for nociception can be achieved by sensory testing using standardized stimuli. Herein, we describe the rationale for and development of an international consortium to better understand and characterize CP pain. METHODS: A collaboration was initially formed between the University of Aalborg, Johns Hopkins University, and the University of Pittsburgh. This group refined the protocol for pancreatic quantitative sensory testing (P-QST) and then expanded the collaboration with plans for incorporating P-QST into prospective studies. RESULTS: The collaboration has successfully developed a P-QST nomogram. Chronic pancreatitis patients identified with P-QST as having widespread hyperalgesia had higher pain intensity scores, higher prevalence of constant pain, and decreased quality of life. Psychiatric comorbidities were independent of pain phenotypes. Multiple studies are underway to validate these findings and evaluate their utility in clinical trials. CONCLUSIONS: Development of the P-QST Consortium will facilitate collaborative efforts to use P-QST as a means for evaluation and characterization of pain in CP patients, and optimize methods to guide individualized pain management approaches.

Chronic binge alcohol and ovariectomy-mediated impaired insulin responsiveness in SIV-infected female rhesus macaques.

Aging people living with HIV (PLWH), especially postmenopausal women may be at higher risk of comorbidities associated with HIV, antiretroviral therapy (ART), hypogonadism, and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-ß in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX) on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Female macaques were administered CBA (12-15 g/kg/wk) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIVmac251, and initiated on antiretroviral therapy (ART) 2.5 mo postinfection. After 1 mo of ART, macaques were randomized to OVX or sham surgeries (n = 7 or 8/group), and euthanized 8 mo post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected time points. Pancreatic gene expression and islet morphology were determined at study endpoint. There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG (P = 0.06). CBA and OVX decreased the expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction that may be exacerbated by alcohol use and ovarian hormone loss.

Exocrine pancreatic function and dynamic of digestion after restrictive and malabsorptive bariatric surgery: a prospective, cross-sectional, and comparative study.

BACKGROUND: Gastrointestinal anatomical changes after restrictive and malabsorptive bariatric surgery lead to important disturbances in the process of digestion and absorption of nutrients and could lead to exocrine pancreatic insufficiency (EPI). OBJECTIVE: The aim of the present study was to evaluate and to compare pancreatic function and the dynamic of digestion and absorption of nutrients after restrictive and malabsorptive bariatric surgical procedures. SETTING: University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. METHODS: A prospective, observational, cross-sectional, comparative study of patients after sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with duodenal switch (BPD/DS) was carried out. Patients with obesity who did not undergo surgery were included as control group. Pancreatic function and the dynamic of digestion and absorption of nutrients were evaluated by the 13C-mixed triglyceride (13C-MTG) breath test. Six-hour 13C-cumulative recovery rate (13C-CRR), 13C exhalation peak, and 1-hour maximal 13C-CRR were calculated. RESULTS: One-hundred five patients were included (mean age, 49.8 yr; 84 women). Six-hour 13C-CRR was significantly reduced after BPD/DS (P < .001) but not after SG and RYGB. EPI was present in 75% of patients after BPD/DS, 8.3% of patients after RYGB, and 4.3% of patients after SG. Compared with the control group who did not undergo surgery, digestion and absorption of nutrients tended to occur earlier after SG, whereas it was delayed after RYGB and mainly after BPD/DS (P < .001). CONCLUSION: Bariatric surgery significantly alters the dynamic of the digestive process. EPI is very common after BPD/DS, frequent after RYGB, and less frequent after SG. This information is clinically relevant since EPI is a treatable condition associated with symptoms, nutritional deficiencies, and complications.

The course and prognostic value of increased pancreas stiffness detected by ultrasound elastography during acute pancreatitis.

BACKGROUND: In this study, we determined the pancreatic stiffness (PS) changes in the course of acute pancreatitis (AP) by ultrasound elastography and evaluated its relation with prognosis. MATERIAL/METHODS: Pancreatic shear wave velocity measurements (SWM) were evaluated at the time of admission to the hospital, following clinical improvement, and one-month after for AP patients and compared to healthy volunteers. Its relationship with clinical severity indexes was evaluated. RESULTS: The pancreatic SWM value in the healthy group was 7.72 ± 2.50 kPa, and in AP group was 10.97 ± 2.26 kPa (p = 0.000). There was no difference between mild and severe pancreatitis. The mean SWM was 8.96 ± 1.53 kPa after disease remission, and 8.83 ± 1.24 kPa after 1-month. CONCLUSIONS: PS increases significantly during AP and decreases with clinical improvement, but this was still higher than controls, and it kept its elevation after 1-month. We think that larger, long-term studies are needed to determine the clinicopathological significance of this.

A randomised, multicentre trial of somatostatin to prevent clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy.

BACKGROUND: Prophylactic somatostatin to reduce the incidence of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy remains controversial. We assessed the preventive efficacy of somatostatin on clinically relevant postoperative pancreatic fistula in intermediate-risk patients who underwent pancreaticoduodenectomy at pancreatic centres in China. METHODS: In this multicentre, prospective, randomised controlled trial, we used the updated postoperative pancreatic fistula classification criteria and cases were confirmed by an independent data monitoring committee to improve comparability between centres. The primary endpoint was the rate of clinically relevant postoperative pancreatic fistula within 30 days after pancreaticoduodenectomy. RESULTS: Eligible patients (randomised, n = 205; final analysis, n = 199) were randomised to receive postoperative intravenous somatostatin (250 µg/h over 120 h; n = 99) or conventional therapy (n = 100). The primary endpoint was significantly lower in the somatostatin vs control group (n = 13 vs n = 25; 13% vs 25%, P = 0.032). There were no significant differences for biochemical leak (P = 0.289), biliary fistula (P = 0.986), abdominal infection (P = 0.829), chylous fistula (P = 0.748), late postoperative haemorrhage (P = 0.237), mean length of hospital stay (P = 0.512), medical costs (P = 0.917), reoperation rate (P > 0.99), or 30 days' readmission rate (P = 0.361). The somatostatin group had a higher rate of delayed gastric emptying vs control (n = 33 vs n = 21; 33% vs 21%, P = 0.050). CONCLUSIONS: Prophylactic somatostatin treatment reduced clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy. TRIAL REGISTRATION: NCT03349424.

Comparison between prognostic indicators in organ insufficiency with acute pancreatitis.

BACKGROUND: Organ failures that develop due to acute pancreatitis (AP), some laboratory values and the anthropometric characteristics of the patients have been shown to play a role in the prognosis AP and have been increasingly used to investigate the prognosis of the disease although classification systems, such as Ranson's criteria, are still used habitually. In this stud, we aimed to investigate the relationship of the organ failures observed during the course of AP, the biochemical parameters and the anthropometric characteristics of the patients and compare using Ranson's and Atlanta Classifica-tion (AC) systems. METHODS: Laboratory values, anthropometric data, including the waist circumference and body mass index, Systemic inflammatory response syndrome (SIRS) and organ failures developed during the course of the disease, were investigated prospectively in 153 AP patients and the Ranson and Modified Atlanta Classifications (MAC) were made. RESULTS: A relationship was observed between the organ failures that were established in the course of the disease (lung, liver, kidney, heart and MOF (multiple organ failure)) and higher Ranson's and MAC scores (p<0.05). Among the patients included in this study, 13 (8.4%) had multiple organ failure and 17 (11.1%) had SIRS. Exitus occurred in 10 patients (6.5%). A statistically significant relationship was found with organ failure, multiple organ failure and SIRS; and ensuing exitus (p<0.05). While no relationship was observed between the waist circumference, body mass index, Ranson's score, there was a significant relationship between the MAC and the waist circumference (p<0.01). Among the laboratory values, high urea and ALT values showed a relationship with the Ranson and MAC (p<0.001), while between the CRP values tested at the 0 time point and the 48th hour, only the CRP value at the 48th hour had a relationship with Ranson's score (p<0.05). Organ failure, MOF, and SIRS showed a correlation with both the severity scores and the mortality rate. In addition, a significant corre-lation was observed between the cholesterol, triglycerides and the CRP level at the time of hospitalisa-tion and mortality. On the contrary, no significant relationship was observed with the other laboratory results, including calcium, lipase and hematocrit. CONCLUSION: In conclusion, to determine the severity and prognosis of acute pancreatitis, and ex-pect the organ failures that may occur in severe pancreatitis, the body mass index, waist circumference and laboratory values, including cholesterol, triglycerides, ALT, and CRP may supply important prog-nostic data besides the conventional disease severity scoring methods.

COVID-19 in gastroenterology: Where are we now? Current evidence on the impact of COVID-19 in gastroenterology.

BACKGROUND: The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. OBJECTIVE: At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. METHODS/RESULTS/CONCLUSION: We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

Optical Imaging of Pancreatic Innervation.

At the time of Ivan Pavlov, pancreatic innervation was studied by looking at pancreas secretions in response to electrical stimulation of nerves. Nowadays we have ways to visualize neuronal activity in real time thanks to advances in fluorescent reporters and imaging techniques. We also have very precise optogenetic and pharmacogenetic approaches that allow neuronal manipulations in a very specific manner. These technological advances have been extensively employed for studying the central nervous system and are just beginning to be incorporated for studying visceral innervation. Pancreatic innervation is complex, and the role it plays in physiology and pathophysiology of the organ is still not fully understood. In this review we highlight anatomical aspects of pancreatic innervation, techniques for pancreatic neuronal labeling, and approaches for imaging pancreatic innervation in vitro and in vivo.

The Effect of Preoperative Biliary Drainage with or without Pancreatic Stenting on Complications after Pancreatoduodenectomy: A Retrospective Cohort Study.

BACKGROUND: The necessity of preoperative biliary drainage (PBD) prior to pancreaticoduodenectomy (PD) is still controversial. However, in some settings, PBD with endoscopic retrograde cholangiopancreatography (ERCP) procedure is recommended as a preferred management. Meanwhile, pancreatic duct stenting in the drainage procedure is rarely performed for selected indications, and its associated complications after PD remain quite unknown. METHODS: A retrospective observational longitudinal cohort study was performed on patients who underwent PBD and PD from a prospectively maintained database at the National Cancer Center from March of 2015 to July of 2019. Patients who underwent biliary stenting alone, biliary and pancreatic stenting, were distributed into two study cohort groups, and their records were scrutinized for the incidence of postoperative complications. RESULTS: A total of 83 patients who underwent successful PD after biliary drainage were identified. 29 patients underwent nasobiliary drainage (ENBD)/plastic or metal bile duct stenting (BS) and pancreatic duct stenting (PS group), and 54 patients underwent only ENBD/BS, without pancreatic duct stenting (NPS group). No differences were found between the two groups with respect to in-hospital time, overall complication rate, respective rate of serious (grade 3 or higher) complication rate, bile anastomotic leakage, bleeding, abdominal infection, surgical wound infection, organ dysfunction, and pancreatic anastomotic leakage. Postoperative gastrointestinal dysfunction rates differed significantly, which occurred in 3 (5.56%) cases in the NPS group, compared with 6 (20.7%) cases in the PS group (P = 0.06). In the univariate and multivariate regression model analysis, pancreatic duct stenting was correlated with higher rates of gastrointestinal dysfunction [odds ratio (OR) = 4.25, P = 0.0472]. CONCLUSION: Our data suggested that PBD and pancreatic duct stenting prior to pancreatoduodenectomy would increase the risk of postoperative delayed gastric emptying, while the overall incidence of postoperative complications and other complications, such as pancreatic leakage and bile duct leakage, showed no statistical difference.

Inulin Fermentable Fiber Ameliorates Type I Diabetes via IL22 and Short-Chain Fatty Acids in Experimental Models.

BACKGROUND & AIMS: Nourishment of gut microbiota via consumption of fermentable fiber promotes gut health and guards against metabolic syndrome. In contrast, how dietary fiber impacts type 1 diabetes is less clear. METHODS: To examine impact of dietary fibers on development of type 1 diabetes in the streptozotocin (STZ)-induced and spontaneous non-obese diabetes (NOD) models, mice were fed grain-based chow (GBC) or compositionally defined diets enriched with a fermentable fiber (inulin) or an insoluble fiber (cellulose). Spontaneous (NOD mice) or STZ-induced (wild-type mice) diabetes was monitored. RESULTS: Relative to GBC, low-fiber diets exacerbated STZ-induced diabetes, whereas diets enriched with inulin, but not cellulose, strongly protected against or treated it. Inulin's restoration of glycemic control prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin's beneficial impact on glycemic control, indicating a role for short-chain fatty acids (SCFA). Furthermore, inulin's microbiota-dependent anti-diabetic effect associated with SCFA-independent restoration of interleukin 22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Inulin-enriched diets significantly delayed diabetes in NOD mice. CONCLUSIONS: Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes.

Increased canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase in dogs with evidence of portal hypertension and normal pancreatic histology: a pilot study.

The clinical presentations of both liver disease and pancreatitis are nonspecific and overlapping, which may cause difficulty in diagnosis. In our retrospective pilot study, we assessed whether dogs with evidence of portal hypertension and absence of pancreatitis on pancreatic histology have increases in canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase. We included dogs that had been presented between 2008 and 2019 if they had normal pancreatic histology, histologically confirmed hepatopathy, and if canine pancreas-specific lipase (Spec cPL; Idexx) or DGGR lipase had been measured. Only dogs with portal hypertension were included. Six dogs fulfilled the inclusion criteria. Four of 6 and 2 of 6 dogs had Spec cPL and DGGR lipase exceeding the upper reference limit, respectively. From the 4 dogs with increased Spec cPL, 2 had concentrations of 200-400 µg/L and 2 had concentrations ≥ 400 µg/L. Our results suggest that canine portal hypertension might lead to increased Spec cPL and DGGR lipase values in the absence of pancreatitis on histology. Until more evidence in a larger number of dogs with portal hypertension is available, both tests should be interpreted cautiously in the presence of portal hypertension.

Role of serotonin in regulation of pancreatic and mesenteric arterial function in diabetic mice.

The aim of this study was to investigate the reaction of pancreatic and mesenteric artery to 5-hydroxytryptamine (5-HT, serotonin) and the mechanism of nitric oxide in diabetes. Diabetic mice were induced by streptozotocin through intraperitoneal injection. The vascular tension of the pancreatic, mesenteric and brain basilar arteries in diabetic and control mice were measured by myograph in the applications of angiotensin II, 5-HT, 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), 5-HT1B/1D receptor agonist sumatriptan, 5-HT2B receptor agonist BW723C86, 5-HT1D receptor antagonist Palonosetron and 5-HT2 receptor antagonist Sarpogrelate. The effect of 5-HT on arteries pretreated with L-NAME and sodium nitroprusside (SNP) on arteries pretreated with norepinephrine were measured. The mRNA expressions of eNOS, 5-HT1B, 5-HT1D, 5-HT2A and 5-HT2B in pancreatic and mesenteric arteries were measured by Real-time PCR. The concentration of 5-HT in plasma and eNOS in pancreatic and mesenteric arteries were tested. Our results showed that the tension of pancreatic and mesenteric arteries in diabetic mice impaired to 5-HT, but not Ang II, and to DOI and sumatriptan, but normalized by incubation with L-NAME. Pancreatic and mesenteric arteries showed no differences to SNP after pretreated with NE between diabetic and control mice. The mRNA of eNOS and 5-HT receptors in pancreatic and mesenteric artery showed no difference between control and diabetic mice. We conclude that the effect of 5-HT on the tension of pancreatic and mesenteric arteries decrease in diabetic mice. It may due to the decreased activity of 5-HT receptors and the activation of eNOS, which causes nitric oxide to release more and makes the tension of vessels decreased.