Severe acute malnutrition may lead both concurrently and subsequently to malabsorption and impaired glucose metabolism from pancreatic dysfunction. We conducted a systematic review to investigate the associations of current and prior postnatal wasting malnutrition with pancreatic endocrine and exocrine functions in humans. We searched PubMed, Google Scholar, Web of Science and reference lists of retrieved articles, limited to articles in English published before 1 February 2022. We included sixty-eight articles, mostly cross-sectional or cohort studies from twenty-nine countries including 592 530 participants, of which 325 998 were from a single study. Many were small clinical studies from decades ago and rated poor quality. Exocrine pancreas function, indicated by duodenal fluid or serum enzymes, or faecal elastase, was generally impaired in malnutrition. Insulin production was usually low in malnourished children and adults. Glucose disappearance during oral and intravenous glucose tolerance tests was variable. Upon treatment of malnutrition, most abnormalities improved but frequently not to control levels. Famine survivors studied decades later showed ongoing impaired glucose tolerance with some evidence of sex differences. The similar findings from anorexia nervosa, famine survivors and poverty- or infection-associated malnutrition in low- and middle-income countries (LMIC) lend credence to results being due to malnutrition itself. Research using large, well-documented cohorts and considering sexes separately, is needed to improve prevention and treatment of exocrine and endocrine pancreas abnormalities in LMIC with a high burden of malnutrition and diabetes.

Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59 774 people aged 40–79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v. no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.

Pancreatic eurytrematosis (PE) is an under diagnosed and neglected parasitosis in goats and sheep in the Americas. Clinical and pathological features of PE are not well defined in small ruminants worldwide. Natural cases of PE in small ruminants were detected in the Federal District, Brazil. A survey of necropsy records, including epidemiological and clinicopathological data, in goats and sheep was conducted. Most cases of PE occurred during the rainy season in adult females, with an incidence of 12.9% in goats and 0.8% in sheep. Clinical signs varied from asymptomatic infections to anorexia, lethargy, weakness, marked weight loss and death in some goats. Overall, most cases of PE in goats and sheep were incidental necropsy findings with minor pancreatic lesions. Three goats, however, showed severe chronic pancreatitis, dilation of major pancreatic ducts with numerous trematodes present and marked abdominal fat necrosis. Morphological and molecular characterization of flukes detected Eurytrema coelomaticum. Our findings shed light on the prevalence of E. coelomaticum infections in small ruminants in the region and highlight the possibility of severe and lethal cases in goats. PE must be further investigated in small ruminant populations in relevant livestock production regions of the Americas.

Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.

This study investigated the effects of short-term subclinical Zn deficiency on exocrine pancreatic activity and changes in digestive capacity. A total of forty-eight weaned piglets were fed ad libitum a basal diet (maize and soyabean meal) with adequate Zn supply (88 mg Zn/kg diet) during a 2-week acclimatisation phase. Animals were then assigned to eight dietary treatment groups (n 6) according to a complete randomised block design considering litter, live weight and sex. All pigs were fed restrictively (450 g diet/d) the basal diet but with varying ZnSO4.7H2O additions, resulting in 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8 and 88·0 mg Zn/kg diet for a total experimental period of 8 d. Pancreatic Zn concentrations and pancreatic activities of trypsin, chymotrypsin, carboxypeptidase A and B, elastase and α-amylase exhibited a broken-line response to stepwise reduction in dietary Zn by declining beneath thresholds of 39·0, 58·0, 58·0, 41·2, 47·5, 57·7 and 58·0 mg Zn/kg diet, respectively. Furthermore, carboxypeptidase B and α-amylase activities were significantly lower in samples with reduced pancreatic Zn contents. Coefficients of faecal digestibility of DM, crude protein, total lipids and crude ash responded similarly to pancreatic enzyme activities by declining below dietary thresholds of 54·7, 45·0, 46·9 and 58·2 mg Zn/kg diet, respectively. In conclusion, (1) subclinical Zn deficiency impaired pancreatic exocrine enzymes, (2) this response was connected to pancreatic Zn metabolism and (3) the decline in catalytic activity impaired faecal digestibility already after 1 week of insufficient alimentary Zn supply and very early before clinical deficiency symptoms arise.

Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses had more (P<0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters (P⩽0.02). Larger insulin-containing clusters were observed in fetuses (P<0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased α-amylase content. Nutrient restriction decreased the number of pancreatic insulin-containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial.

Recent studies have shown that ghrelin increases pancreatic exocrine secretion. However, the potential effects of ghrelin on the morphology of exocrine pancreas (EP) remain unknown. In this work, using fractal analysis, we demonstrate that centrally administered ghrelin increases structural complexity and tissue disorder in rat EP. The study was carried out on a total of 40 male Wistar rats divided into four groups (n = 10): ghrelin-treated animals (average age, 1.5 months), ghrelin-treated animals (8.5 months), and controls (1.5 and 8.5 months). The pancreas tissue sections were stained with hematoxylin/eosin and visualized by light microscopy. For each animal, the average values of tissue fractal dimension, lacunarity, as well as parameters of co-occurrence matrix texture, were determined using tissue digital micrographs. The results indicate that ghrelin administration increases EP fractal dimension and textural entropy, and decreases lacunarity, regardless of the age. To our knowledge, this is the first study to investigate the effects of ghrelin on the morphological properties of pancreatic tissue, and also the first to apply fractal and textural analysis methods in quantification of EP tissue architecture.

In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced β-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory β-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 ± 211 v. 292 ± 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 ± 0.03 v. 1.08 ± 0.06 ng/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 ± 0.11 ng/ml; P < 0.05) but decreased GSIS in controls (0.86 ± 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory β-cell stimulus-secretion responsiveness is present before IUGR.

Diabetes predisposition is determined by pancreatic islet insulin secretion and insulin resistance. We studied female rat offspring exposed to low-protein maternal diet (50% control protein diet) in pregnancy and/or lactation at postnatal days 36, 110 and 450. Rats were fed either control 20% casein diet (C) or restricted diet (R – 10% casein) during pregnancy. After delivery, mothers received either C or R diet until weaning to provide four offspring groups: CC, RR, CR and RC (first letter denoting maternal pregnancy diet and the second lactation diet). Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low glucose (5 mM) and high glucose (11 mM). Serum glucose, insulin and HOMA were similar in all groups at 36 and 110 postnatal days. HOMA was only higher in RR at 450 postnatal days. Only CC demonstrated differences in glucose sensitivity of β-cells to high and low doses at the three ages studied. At 36 days, RR, CR and RC and at 450 days RR and RC groups did not show glucose-stimulated insulin secretion differences between low and high glucose. Aging-associated glucose-stimulated insulin secretion loss was affected by maternal dietary history, indicating that developmental programming must be considered a major factor in aging-related development of predisposition to later-life dysfunctional insulin metabolism. Female offspring islets’ insulin secretion was higher than previously reported in males.

The aim of the present study was to determine the effects of a cafeteria diet on the function and apoptosis of the pancreas, and the activity and expression of the insulin-degrading enzyme (IDE). Female Wistar rats were fed either with a cafeteria diet or a control diet for 17 weeks, and blood and tissues were then collected for analysis. The cafeteria diet-treated rats had higher plasma insulin and C-peptide levels (P < 0·05), showing increased insulin secretion by the pancreas. Insulin protein and gene expression levels were higher in the pancreas of obese rats, as was its transcriptional controller, pancreatic duodenal homeobox 1 (P < 0·05). Feeding a cafeteria diet down-regulated the gene expression of the anti-apoptotic marker B-cell/lymphoma 2 (BCL2), and up-regulated the protein levels of BCL2-associated X protein, a pro-apoptotic marker (P < 0·05). The cafeteria diet caused lipid accumulation in the pancreas and modified the expression of key genes that control lipid metabolism. To assay whether insulin clearance was also modified, we checked the activity of the IDE, one of the enzymes responsible for insulin clearance. We found increased liver IDE activity (P < 0·05) in the cafeteria diet-fed animals, which could, in part, be due to an up-regulation of its gene expression. Conversely, IDE gene expression was unmodified in the kidney and adipose tissue; although when the adipose tissue weight was considered, the insulin clearance potential was higher in the cafeteria diet-treated rats. In conclusion, treatment with a cafeteria diet for 17 weeks in rats mimicked a pre-diabetic state, with ectopic lipid accumulation in the pancreas, and increased the IDE-mediated insulin clearance capability.

The pancreatic enzyme secretory phospholipase A2 group IB (sPLA2 IB) hydrolyses phospholipids at the sn-2 position, resulting in a NEFA and a lyso-phospholipid, which are then absorbed by the enterocytes. The sPLA2 IB is a member of a family of nineteen enzymes sharing the same catalytic ability, of which nine are cytosolic and ten are secretory. Presently, there are no pharmacological tools to separate between the different secretory enzymes when measuring the enzymatic activity. Thus, it is important to support activity data with more precise techniques when isolation of intestinal content is not possible for analysis, as in the case of small teleost larvae, where the whole animal is sometimes analysed. In the present study, we characterise the sPLA2 IB gene in Atlantic cod (Gadus morhua) and describe its ontogeny at the genetic and protein level and compare this to the total sPLA2 activity level. A positive correlation was found between the expression of sPLA2 IB mRNA and protein. Both remained stable and low during the larval stage followed by an increase from day 62 posthatch, coinciding with the development of the pyloric ceaca. Meanwhile, total sPLA2 enzyme activity in cod was stable and relatively high during the early stages when larvae were fed live prey, followed by a decrease in activity when the fish were weaned to a formulated diet. Thus, the expression of sPLA2 IB mRNA and protein did not correlate with total sPLA2 activity.

The three-dimensional (3D) keratin filament network of pancreatic carcinoma cells was investigated with different electron microscopical approaches. Semithin sections of high-pressure frozen and freeze substituted cells were analyzed with scanning transmission electron microscope (STEM) tomography. Preservation of subcellular structures was excellent, and keratin filaments could be observed; however, it was impossible to three-dimensionally track the individual filaments. To obtain a better signal-to-noise ratio in transmission mode, we observed ultrathin sections of high-pressure frozen and freeze substituted samples with low-voltage (30 kV) STEM. Contrast was improved compared to 300 kV, and individual filaments could be observed. The filament network of samples prepared by detergent extraction was imaged by high-resolution scanning electron microscopy (SEM) with very good signal-to-noise ratio using the secondary electron signal and the 3D structure could be elucidated by SEM tomography. In freeze-dried samples it was possible to discern between keratin filaments and actin filaments because the helical arrangement of actin subunits in the F-actin could be resolved. When comparing the network structures of the differently prepared samples, we found no obvious differences in filament length and branching, indicating that the intermediate filament network is less susceptible to preparation artifacts than the actin network.

Enteral exposure of suckling rats to phytohaemagglutinin (PHA) has been shown to induce growth and precocious functional maturation of the gastrointestinal tract. The aim of the present study was to explore the mechanism of this action. Suckling rats, 14d old, were fed a single dose of PHA (0·05mg/g body weight) or saline. The binding of PHA to the gut epithelium and its effect on the morphology and functional properties of the gut and pancreas were studied up to 3d after treatment. Initially, at 1–24h, the PHA bound along the gut mucosal lining, resulting in disturbed gut morphology with villi shortening and rapid decreases in disaccharidase activities and macromolecular absorption capacity. During a later phase, between 1 and 3d, the PHA binding had declined, and an uptake by enterocytes was observed. An increase in crypt cell proliferation and gut growth became evident during this period, together with a functional maturation, as indicated by increases in disaccharidase (maltase and sucrase) activities and the low macromolecular absorption capacity. Pancreas growth also increased, as did its content of digestive enzymes. We conclude that enteral exposure to PHA in suckling rats temporarily causes mucosal disarrangement and functional impediment of the gut, which may be explained by binding to and disruption of the gut mucosa and a two-fold increase in the plasma corticosterone concentration. These findings may lead to a better understanding of the role of diet in gastrointestinal maturation and may constitute a basis for the treatment of mammals having an immature gut.

Les effets radio-induits sur le pancréas, communément décrits chez les mammifères, concernent essentiellement des modifications structurales observées à long terme. En revanche, peu d'études traitent des conséquences fonctionnelles d'une irradiation sur le pancréas exocrine. Le but de ce travail est de suivre les effets aigus d'une irradiation corps entier sur le volume et l'activité enzymatique du suc pancréatique. Une irradiation gamma corps entier à la dose de 6 Gy a été réalisée chez des porcs. Une collecte de suc pancréatique, par cathétérisme permanent du canal pancréatique, a été réalisée avant et après exposition avec mesure en continu du volume sécrété. Sur chaque échantillon de suc pancréatique, la concentration protéique ainsi que l'activité enzymatique de la trypsine, chymotrypsine, élastase, lipase et amylase ont été déterminées. Le volume de suc pancréatique sécrété quotidiennement diminue dès le lendemain de l'irradiation et le niveau sécrétoire ne revient jamais à des valeurs enregistrées avant irradiation. La quantité de protéines et les activités totales des enzymes sécrétées dans le suc pancréatique sont réduites de manière parallèle. Enfin, seules les activités spécifiques de l'élastase et de la lipase sont modifiées après l'irradiation. Ainsi, les conséquences d'une irradiation corps entier chez le porc se traduisent par une diminution importante et rapide de la sécrétion pancréatique exocrine, affectant à la fois les composantes hydro-bicarbonatée et enzymatique. Ce phénomène pourrait contribuer aux perturbations de la sphère intestinale lors du syndrome aigu d'irradiation mais également générer des effets à plus long terme.

Background and objective: The safety of hypotension induced by sevoflurane and splanchnic organ blood flow remains to be clarified. The aim was to investigate the effects of sevoflurane-induced hypotension on systemic haemodynamics and splanchnic organ blood flows in dogs.

Methods: Mean arterial pressure was maintained at 60 mmHg by increasing sevoflurane concentrations. The renal, hepatic and pancreatic blood flows were measured by using the hydrogen clearance method.

Results: Hypotension induced by sevoflurane resulted in a 50% decrease of mean arterial pressure due to a 30% reduction in systemic vascular resistance associated with a 30% decrease in cardiac index. The mechanisms causing the lower cardiac index were produced by the decreases in heart rate and left ventricular dP/dtmax. Renal, hepatic and pancreatic blood flow were reduced, but the whole-body oxygen consumption did not change during the hypotensive period.

Conclusions: The haemodynamic changes induced by sevoflurane were caused by the suppression of arterial baroreflexes and myocardial depression, but splanchnic organ blood flows, though reduced, could provide adequate peripheral perfusion to meet the decrease in oxygen supply.