Pancreatic Secretory Function Research Articles

Chronic Epinephrine-Induced Endoplasmic Reticulum and Oxidative Stress Impairs Pancreatic β-Cells Function and Fate.

Epinephrine influences the function of pancreatic β-cells, primarily through the α2A-adrenergic receptor (α2A-AR) on their plasma membrane. Previous studies indicate that epinephrine transiently suppresses insulin secretion, whereas prolonged exposure induces its compensatory secretion. Nonetheless, the impact of epinephrine-induced α2A-AR signaling on the survival and function of pancreatic β-cells, particularly the impact of reprogramming after their removal from sustained epinephrine stimulation, remains elusive. In the present study, we applied MIN6, a murine insulinoma cell line, with 3 days of high concentration epinephrine incubation and 2 days of standard incubation, explored cell function and activity, and analyzed relevant regulatory pathways. The results showed that chronic epinephrine incubation led to the desensitization of α2A-AR and enhanced insulin secretion. An increased number of docked insulin granules and impaired Syntaxin-2 was found after chronic epinephrine exposure. Growth curve and cell cycle analyses showed the inhibition of cell proliferation. Transcriptome analysis showed the occurrence of endoplasmic reticulum stress (ER stress) and oxidative stress, such as the presence of BiP, CHOP, IRE1, ATF4, and XBP, affecting cellular endoplasmic reticulum function and survival, along with UCP2, OPA1, PINK, and PRKN, associated with mitochondrial dysfunction. Consequently, we conclude that chronic exposure to epinephrine induces α2A-AR desensitization and leads to ER and oxidative stress, impairing protein processing and mitochondrial function, leading to modified pancreatic β-cell secretory function and cell fate.

Clinical and functional characterization of a novel KCNJ11 (c.101G > A, p.R34H) mutation associated with maturity-onset diabetes mellitus of the young type 13.

This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic β-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.

Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs

BackgroundThe increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. ObjectivesThis study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. MethodsA total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. ResultsHerein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of β-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. ConclusionsUsing fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Excess homocysteine inhibits pancreatic β-cell secretory function by repressing Zbtb20 expression

Homocysteine (Hcy) is a sulfur-containing amino acid. An elevated level of Hcy is a risk factor for diabetes development. However, the mechanism of its effect on pancreatic β-cell function is unclear. In this study, we constructed a hyperhomocysteinemia (HHcy) mouse model by feeding mice a high methionine diet (HMD). The mice suffered impaired glucose tolerance and reduced insulin secretion. Furthermore, at the cellular level, INS1 cells exhibited impaired insulin secretory function after the Hcy intervention. Transcriptomics revealed that Zbtb20 expression was downregulated and the downstream gene Fbp1 was upregulated in HHcy-induced mice compared with mice fed with normal diet. Insulin secretion could be restored by Zbtb20 overexpression or fructose 1,6-bisphosphatase (FBPase) activity inhibition in INS1 cells. In conclusion, our study suggested that Hcy inhibited the insulin secretory function of pancreatic β-cells by suppressing Zbtb20 expression, leading to the development of diabetes. Zbtb20 may be a key target in the development of diabetes associated with elevated Hcy levels.

High-intensity pulse magnetic therapy and drinking mineral water in rehabilitation treatment of patients with chronic pancreatitis at inpatient stage

BACKGROUND: Sanogenetic effects of physical factors, providing restoration of disturbed functions of the organism, are the basis for their inclusion in the standardised programme of restorative treatment of patients with chronic pancreatitis. AIM: To study the effectiveness of high-intensity pulse magnetic therapy and low-mineralized drinking mineral waters in the restorative treatment of patients with chronic pancreatitis at the inpatient stage. MATERIALS AND METHODS: There has been carried out an open-label, randomized, controlled, prospective study of 125 patients with chronic pancreatitis. The patients were divided into 3 groups using the simple randomization method. In the control group (n=40) the patients underwent restorative treatment in accordance with federal clinical guidelines; in the group of comparison (n=42) he patients were additionally prescribed low-mineralized drinking mineral water; in the main group (n=43) the patients had high-intensity pulse magnetic therapy in addition to the treatment of the group of comparison. The effectiveness of rehabilitation measures was monitored using a visual analogue scale, a carbolene test, a hospital scale of anxiety and depression. RESULTS: The statistical analysis showed that the inclusion of drinking mineral water and high-intensity pulse magnetic therapy contributed to a significant reduction of pain (p 0.01) and dyspeptic syndromes (p 0.01), an improvement in motor evacuation function of intestine (p 0.01), a decrease in enzymatic activity and the severity of anxiety-depressive manifestations (p 0.01). The effectiveness of the developed programmes of restorative treatment of the patients suffering from chronic pancreatitis was 87.8–92.5%, the standardized programme ― 78.5%. CONCLUSION: The inclusion of drinking mineral waters and high-intensity pulse magnetic therapy in the standardized program of restorative treatment of the patients suffering from chronic pancreatitis at the inpatient stage provides a significant restoration of pancreatic external secretory function.

Adverse effects of plastic leachate and its component 2,4-DTBP on the early development of zebrafish embryos

Plastic waste has become a global environmental problem threatening the health of aquatic organisms especially via leachate. In this study, the test of zebrafish embryo showed adverse effects of leachate from some agricultural mulching films after UV light aging for 60 h. A typical phenolic antioxidant 2,4-di-tert-butylphenol (2,4-DTBP) was detected in the leachate and tested further for the zebrafish embryo biotoxicity. The microplastic leachate (6, 8 g/L, mass concentration measured by weight of plastic) increased the death and malformation rates, and reduced the hatching rate, heart rate, and body length of zebrafish larvae in the 96-hour early development period. Similar adverse effects were also caused by the 2,4-DTBP (0.01, 0.1, 1.0 mg/L, corresponding to 0.049, 0.49, and 4.85 μM) to some degree but could not completely explain the significant influences caused by the plastic leachate. Transcriptome analysis of zebrafish embryos exposed to the 2,4-DTBP for 96 h showed that the protein, fat, and carbohydrate digestion and absorption pathways, pancreatic secretion, PPAR signaling pathway, tryptophan metabolism, and adipocytokine signaling pathway were considerably down-regulated, but the cholesterol metabolism pathway was up-regulated in larval zebrafish. The altered transcriptional expression of mRNA at early development stage (96 h post fertilization) of zebrafish suggested that the 2,4-DTBP caused reduction of digestive capacity and pancreatic secretory function, and adversely affected processes associated with energy metabolism and glycolipid metabolism of larval zebrafish. This study helps us further understanding the effects of plastic leachate on the early development of fishes.

Gastrectomy reduces pancreatic secretory function via pancreatic atrophy

PurposeAlthough reports suggest that the pancreatic volume decreases after gastrectomy for gastric cancer, the relationship between the pancreatic volume and secretory function after gastrectomy remains unclear. In this study, we examined the relationship between the pancreatic volume and exocrine and endocrine functions after total gastrectomy.MethodsThe pancreatic volumes of 18 distal gastrectomy and 15 total gastrectomy patients were retrospectively measured using computed tomography volumetry up to 5 years postoperatively. Ten low anterior resection patients were selected as controls. In addition, the pancreatic volume and exocrine function evaluated by fecal elastase and the insulin secretory function evaluated by glucagon tolerance testing were prospectively examined before and one year after surgery in nine cases of total gastrectomy.ResultsAfter low anterior resection, the pancreatic volume did not change, but after distal and total gastrectomy, the pancreatic volume decreased continuously until the fifth year. After total gastrectomy, fecal elastase decreased significantly from 865.8 μg/g to 603.2 μg/g in the first year (p = 0.0316), and the insulin secretion capacity also decreased significantly from 3.83 ng/mL to 2.26 ng/mL (p = 0.0019).ConclusionsThe pancreatic volume decreases continuously after gastrectomy for gastric cancer, and the pancreatic exocrine and endocrine functions decrease along with pancreatic atrophy after total gastrectomy.

Gut microbiome dysregulation drives bone damage in broiler tibial dyschondroplasia by disrupting glucose homeostasis

Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut–pancreas axis in bone homoeostasis in TD chickens.

Comparative Study Between Quercus Infectoria Galls Extract and Glimepiride On Pancreas and Some Blood Parameters in Diabetic Rats

Diabetes mellitus (DM) is a metabolic disease involving improperly high blood glucose level, hyperlipidemia and hypoinsulinemia. The aim of current study is to assess and compare the influence of Quercus infectoria galls (QIg) extract and glimepiride on pancreatic β-cells secretory function and serum lipid profile in diabetic rats. In the present study, thirty six male rats were used and divided into six groups (n=6), including negative control, STZ induced diabetic control, treated diabetic rats with glimepiride (200mg/Kg Bw), and treated diabetic rats with different concentrations QIg extract, 200 mg, 400 mg and 800 mg/Kg Bw for 42 days, respectively. At the end of the experiment, all rats were fasted overnight, blood samples were collected for measuring fasting blood glucose, insulin hormone and lipid profile. All rats were then scarified by using chloroform in order to take part of the pancreatic tissue. The results show a significant decrease in blood glucose, total cholesterol, triglycerides, low density lipoprotein, very low-density lipoprotein, HbA1c% with obvious elevation in serum insulin hormone and high-density lipoprotein in diabetic rats treated with QIg extract and glimepiride compared with diabetic untreated group. In addition, high atherogenic index in diabetic rats was significantly reduced by different concentrations of QIg extract and glimepiride. Histopathogical results revealed that there was a significant and dose-dependent morphological restoration in the pancreatic structure damages especially at high dose of the extract. These findings provide a new insight into the role of QIg methanolic extract in maintaining normal blood glucose and adequate pancreatic insulin hormone secretion in diabetic rats, amelioration of dyslipidemia and associated cardiovascular alterations with subsequent improvement in pancreatic structural damages in diabetic rats.

β-Sitosterol Glucoside-Loaded Nanosystem Ameliorates Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Rats.

β-Sitosterol glucoside (SG), isolated from Senecio petasitis (Family Asteraceae), was loaded in self-nanoemulsifying drug delivery systems (SEDDS) in a trial to enhance its solubility and biological effect. Various co-surfactants were tested to prepare a successful SEDDS. The selected SG-loaded SEDDS had a droplet size of 134 ± 15.2 nm with a homogenous distribution (polydispersity index 0.296 ± 0.02). It also demonstrated a significant augmentation of SG in vitro release by 4-fold compared to the free drug suspension. The in vivo insulin sensitivity and antidiabetic effect of the prepared SG-loaded SEDDS were further assessed in streptozotocin-induced hyperglycemic rats. The hypoglycemic effect of SG-loaded nanosystem was evidenced by decreased serum glucose and insulin by 63.22% and 53.11%, respectively. Homeostasis model assessment-insulin resistance (HOMA-IR) index demonstrated a significant reduction by 5.4-fold in the diabetic group treated by SG-loaded nanosystem and exhibited reduced glucagon level by 40.85%. In addition, treatment with SG-loaded nanosystem significantly decreased serum MDA (malondialdehyde) and increased catalase levels by 38.31% and 64.45%, respectively. Histopathological investigations also supported the protective effect of SG-loaded nanosystem on the pancreas. The promising ability of SG-loaded nanosystem to ameliorate insulin resistance, protect against oxidative stress, and restore pancreatic β-cell secretory function warrants its inclusion in further studies during diabetes progression.

Understanding the pathogenesis of lean non-autoimmune diabetes in an African population with newly diagnosed diabetes

Aims/hypothesisApparent type 2 diabetes is increasingly reported in lean adult individuals in sub-Saharan Africa. However, studies undertaking robust clinical and metabolic characterisation of lean individuals with new-onset type 2 diabetes are limited in this population. This cross-sectional study aimed to perform a detailed clinical and metabolic characterisation of newly diagnosed adult patients with diabetes in Uganda, in order to compare features between lean and non-lean individuals.MethodsSocio-demographic, clinical, biophysical and metabolic (including oral glucose tolerance test) data were collected on 568 adult patients with newly diagnosed diabetes. Participants were screened for islet autoantibodies to exclude those with autoimmune diabetes. The remaining participants (with type 2 diabetes) were then classified as lean (BMI <25 kg/m2) or non-lean (BMI ≥25 kg/m2), and their socio-demographic, clinical, biophysical and metabolic characteristics were compared.ResultsThirty-four participants (6.4%) were excluded from analyses because they were positive for pancreatic autoantibodies, and a further 34 participants because they had incomplete data. For the remaining 500 participants, the median (IQR) age, BMI and HbA1c were 48 years (39–58), 27.5 kg/m2 (23.6–31.4) and 90 mmol/mol (61–113) (10.3% [7.7–12.5]), respectively, with a female predominance (approximately 57%). Of the 500 participants, 160 (32%) and 340 (68%) were lean and non-lean, respectively. Compared with non-lean participants, lean participants were mainly male (60.6% vs 35.3%, p<0.001) and had lower visceral adiposity level (5 [4–7] vs 11 [9–13], p<0.001) and features of the metabolic syndrome (uric acid, 246.5 [205.0–290.6] vs 289 [234–347] μmol/l, p<0.001; leptin, 660.9 [174.5–1993.1] vs 3988.0 [1336.0–6595.0] pg/ml, p<0.001). In addition, they displayed markedly reduced markers of beta cell function (oral insulinogenic index 0.8 [0.3–2.5] vs 1.6 [0.6–4.6] pmol/mmol; 120 min serum C-peptide 0.70 [0.33–1.36] vs 1.02 [0.60–1.66] nmol/l, p<0.001).Conclusions/interpretationApproximately one-third of participants with incident adult-onset non-autoimmune diabetes had BMI <25 kg/m2. Diabetes in these lean individuals was more common in men, and predominantly associated with reduced pancreatic secretory function rather than insulin resistance. The underlying pathological mechanisms are unclear, but this is likely to have important management implications.Graphical abstract

Long-term outcomes of pancreatic head resection in chronic pancreatitis

To analyze the effect of timing of surgery, quality of resection and removal of MPD-stones on long-term results of duodenum-preserving pancreatic head resection (DPPHR). The study included 110 patients with chronic pancreatitis (CP) who underwent DPPHR in 2014-2019. Evaluation of long-term outcomes included pain syndrome severity, exocrine and endocrine insufficiency and quality of life (QoL). Patients were stratified depending on duration of disease (within 36 months, >36 months after manifestation), volume of resected pancreatic head tissue according to CT data, removal of MPD-stones. Surgical treatment within 36 months after clinical manifestation was followed by less pain syndrome (VAS score 1.16±1.76 vs. 2.03±1.87, p=0.02), exocrine insufficiency (69.8% vs. 98.5%, p<0.001). Resection of more than 50% of the pancreatic head and removal of MPD-stones were accompanied by pain relief, improved pancreatic secretory function and quality of life. Pancreatic head resection in patients with chronic pancreatitis should be performed within 3 years after clinical manifestation. Resection of more than 50% of the pancreatic head with extraction of MPD-stones ensures pain relief, better endocrine and exocrine function, as well as higher QoL in long-term follow-up period.

Functional Role of the Secretin/Secretin Receptor Signaling During Cholestatic Liver Injury.

The gastrointestinal peptide, secretin (Sct) is an important homeostatic regulator of pancreatic and liver secretory function. With regard to the liver, discoveries have been made, in the last decades, indicating a key role for the secretin/secretin receptor axis during normal or cholestatic conditions. Since large cholangiocytes are the only cells to express secretin receptor in the liver, research on secretin also expanded our knowledge on biliary epithelia. In this review we examined in detail the role of the secretin/secretin receptor axis, not only on biliary secretion, but also on cholangiocyte proliferation and senescence, as well as in prompting fibrotic processes involving biliary epithelia. Relevant data on human chronic cholestatic liver diseases, such as primary biliary cholangitis or primary sclerosing cholangitis, and obtained in animal models mimicking the diseases or in correlative studies on human are also reported. The aim of this review is to provide an update on the progress regarding the interactions between secretin and the biliary epithelia in normal and pathological conditions, underlining the aspects that suggests modulation of secretin pathway as a possible therapeutic approach for chronic cholestatic human liver disease.

Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole-body glucose homeostasis: does it actually work in humans?

Nicotinamide riboside supplementation to improve skeletal muscle mitochondrial health and whole-body glucose homeostasis: does it actually work in humans?

Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus - A Small Cross-Sectional Study

Loss of Pancreatic β-cell Secretory Function During Disease Progression in Type 2 Diabetes Mellitus - A Small Cross-Sectional Study

Vasopressin receptors in islets enhance glucose tolerance, pancreatic beta-cell secretory function, proliferation and survival

Arginine vasopressin (AVP), a peptide secreted from the posterior pituitary, is chiefly regarded as a hormone involved in the regulation of body fluid balance and osmolality. However, recent evidence has revealed that posterior pituitary hormones can exert important actions on endocrine pancreatic function. In the present study, the presence of AVP receptors, namely Avpr1a (V1a), Avpr1b (V1b) and Avpr2 (V2) was demonstrated in murine islets as well as rodent BRIN BD11 and human 1.1B4 beta-cells. Further to this, AVP was shown to induce significant concentration-dependent (10−12 – 10−6 M) increases of insulin release from both rodent and human beta-cells, as well as mouse islets. Insulinotropic actions of AVP were completely annulled by specific V1a or V1b receptor antagonists, and partially abolished by an oxytocin receptor antagonist. In addition, beta-cell insulin secretory actions of AVP were augmented by both IBMX (200 μM) and KCl (30 mM) and linked to significantly increased cAMP production and [Ca2+]i. AVP substantially increased proliferation of rodent and human beta-cells. Moreover, AVP fully protected against cytokine-induced beta-cell apoptosis. AVP had no effect on glucagon secretion. Immunohistochemical examination of beta- and alpha-cells revealed co-expression of AVP with glucagon, and particularly insulin. Finally, administration of AVP in combination with glucose to mice significantly reduced blood glucose, which was associated with increased plasma insulin. These data indicate that AVP possesses novel and potentially important effects on pancreatic endocrine function. Understanding disturbances in islet AVP receptor signalling could reveal insight into the beta-cell defects associated with diabetes.

PYY plays a key role in the resolution of diabetes following bariatric surgery in humans.

BackgroundBariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied.MethodsChanges in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22.FindingsWe demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release.InterpretationThis study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction.

Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis

Recently, diabetic gastroparesis (DGP) has received much attention as its prevalence is increasing in a dramatic fashion and management of patients with DGP represents a challenge in the clinical practice due to the limited therapeutic options. DGP highlights an interrelationship between the gastric emptying and pancreatic secretory function that regulate a wide range of digestive and metabolic functions, respectively. It well documented that both gastric emptying and pancreatic secretion are under delicate control by multiple neurohormonal mechanisms including extrinsic parasympathetic pathways and gastrointestinal (GI) hormones. Interestingly, the latter released in response to various determinants that related to the rate and quality of gastric emptying. Others and we have provided strong evidence that the central autonomic nuclei send a dual output (excitatory and inhibitory) to the stomach and the pancreas in response to a variety of hormonal signals from the abdominal viscera. Most of these hormones released upon gastric emptying to provide feedback, and control this process and simultaneously regulate pancreatic secretion and postprandial glycemia. These findings emphasize an important link between gastric emptying and pancreatic secretion and its role in maintaining homeostatic processes within the GI tract. The present review deals with the neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function that implicated in DGP and this provides new insights in our understanding of the pathophysiology of DGP. This also enhances the process of identifying potential therapeutic targets to treat DGP and limit the complications of current management practices.

Prospective Assessment of Normal Pancreatic Secretory Function Measured by MRI in a Cohort of Healthy Children.

Magnetic resonance imaging (MRI) with secretin stimulation promises to allow non-invasive testing for exocrine pancreatic insufficiency but normal data do not exist for children. The purpose of this study was to define, in healthy children, normal pancreatic secreted fluid volume and secretion rate, measured by MRI, in response to secretin. In this Institutional Review Board-approved, prospective, cross-sectional study, 50 healthy children ages 6 to <16 years underwent MRI with secretin stimulation. Images were obtained before and at 1, 5, 10 and 15 min after secretin administration to calculate total secreted fluid volume and secretion rate based on image segmentation. Regression was used to define the relationship between secretory function and participant size measures, and linear quantile regression was used to define normal secretory values based on size measures. Median total secreted fluid volume post secretin was 79 mL (range: 32-162 mL; 5th and 95th percentiles: 43 and 123 mL) and median secretion rate was 5.1 mL/min (range: 2-9.4 mL/min; 5th and 95th percentiles: 2.3 and 7.7 mL/min). Secreted volume and secretion rate had the strongest correlation with body surface area (BSA) (r = 0.54 and 0.59, respectively) and multiple regression defined BSA as the only significant predictor of secretory function. Each 1 m2 increase in BSA was associated with a 38 mL increase in secreted fluid volume. In children, pancreatic secretory response to secretin, measured by MRI, depends on participant size, particularly BSA. Secreted volume <43 mL or a secretion rate <2.3 mL/min (5th percentile values) can be considered abnormal for children.

Secretin-Enhanced Magnetic Resonance Cholangiopancreatography for Assessing Pancreatic Secretory Function in Children

To assess the accuracy and interrater reproducibility of measurements of pancreatic secretory function by magnetic resonance cholangiopancreatography in response to secretin administration and to describe our experience using the technique to noninvasively assess pancreatic secretory function in a pediatric population. In the accuracy study, phantoms with varying fluid volume (47-206 mL) were imaged using the clinical quantification sequence. Fluid volume was measured by image segmentation (ImageJ). Measurement accuracy was expressed in terms of error (absolute and percent) relative to known fluid volume. In the reproducibility study and clinical experience, 31 patients with suspected pancreatic disease underwent 33 secretin-enhanced magnetic resonance cholangiopancreatography exams. Two-dimensional T2-weighted, fat-saturated single shot fast spin echo sequences were acquired before and after secretin injection (0.2 µg/kg, max 16 µg). Secreted fluid volume (postsecretin minus presecretin) was independently measured by 2 blinded reviewers. Between reviewer measurement reproducibility was assessed based on correlation (Spearman) and bias (Bland-Altman analysis). For the accuracy study, fluid volumes were measured with mean volume errors of -0.3 to +12.5 mL (percent error -0.03% to +9.0%). For the reproducibility study, the mean secreted fluid volumes measured by reviewer 1 and reviewer 2 were 79.1 ± 54.3 mL (range 5.5-215.4) and 77.2 ± 47.1 mL (range 6.7-198.1 mL), respectively. Measured secreted fluid volumes were very strongly correlated (r = 0.922) between reviewers with a bias of only 1.9 mL (95% limits of agreement -40.5 to 44.2). Measurement of fluid volume by magnetic resonance imaging is highly accurate with <10% (<13 mL) error in measured volume. Measurements of pancreatic secreted fluid volume in response to secretin by magnetic resonance cholangiopancreatography are highly reproducible with a bias of <2 mL between reviewers.