RESUMEN

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Asunto(s)

Antraquinonas , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Inhibidores Enzimáticos , Lipasa , Páncreas , Relación Estructura-Actividad , Antraquinonas/farmacología , Antraquinonas/química , Antraquinonas/síntesis química , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Humanos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Páncreas/enzimología , Simulación del Acoplamiento Molecular , Productos Biológicos/farmacología , Productos Biológicos/química , Productos Biológicos/síntesis química

RESUMEN

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa-Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

Asunto(s)

Glucuronidasa , Pancreatitis , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/patología , Ratones , Glucuronidasa/metabolismo , Glucuronidasa/antagonistas & inhibidores , Trehalosa/farmacología , Trehalosa/uso terapéutico , Ceruletida , Aspirina/farmacología , Aspirina/uso terapéutico , Modelos Animales de Enfermedad , Enfermedad Aguda , Autofagia/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/patología , Páncreas/enzimología , Masculino , Ratones Transgénicos , Lipasa/metabolismo , Lipasa/antagonistas & inhibidores , Amilasas/sangre , Ratones Endogámicos C57BL , Saponinas

RESUMEN

The detailed characterization of the structural features of peptides targeting cholesterol esterase (CEase) or pancreatic lipase (PPL) will benefit the management of hyperlipidemia and obesity. This study employed the Glide SP (standard precision)-peptide method to predict the binding modes of 202 dipeptides and 203 tripeptides to these targets, correlating residue composition and position with binding energy. Strong preferences for Trp, Phe, and Tyr were observed at all positions of potential inhibitory peptides, whereas negatively charged residues Glu and Asp were disfavored. Notably, Arg and aromatic rings significantly influenced the peptide conformation at the active site. Tripeptide IWR demonstrated the high efficacy, with IC50 values of 0.214 mg/mL for CEase and 0.230 mg/mL for PPL. Five novel IWR scaffold-tetrapeptides exhibited promising inhibitory activity. Non-covalent interactions and energy contributions dominated the formation of stable complexes. Our results provide insights for the development of new sequences or peptide-like molecules with enhanced inhibitory activity.

Asunto(s)

Inhibidores Enzimáticos , Lipasa , Péptidos , Esterol Esterasa , Esterol Esterasa/química , Esterol Esterasa/antagonistas & inhibidores , Esterol Esterasa/metabolismo , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Lipasa/química , Lipasa/antagonistas & inhibidores , Péptidos/química , Péptidos/farmacología , Humanos , Páncreas/enzimología , Páncreas/química , Animales , Simulación del Acoplamiento Molecular

RESUMEN

A variety of therapeutic possibilities have emerged for skillfully regulating protein function or conformation through intermolecular interaction modulation to rectify abnormal biochemical reactions in diseases. Herein, a devised strategy of enzyme coordinators has been employed to alleviate postoperative pancreatic fistula (POPF), which is characterized by the leakage of digestive enzymes including trypsin, chymotrypsin, and lipase. The development of a dextrorotary (D)-peptide supramolecular gel (CP-CNDS) under this notion showcases its propensity for forming gels driven by intermolecular interaction. Upon POPF, CP-CNDS not only captures enzymes from solution into hydrogel, but also effectively entraps them within the internal gel, preventing their exchange with counterparts in the external milieu. As a result, CP-CNDS completely suppresses the activity of digestive enzymes, effectively alleviating POPF. Remarkably, rats with POPF treated with CP-CNDS not only survived but also made a recovery within a mere 3-day period, while mock-treated POPF rats had a survival rate of less than 5 days when experiencing postoperative pancreatic fistula, leak or abscess. Collectively, the reported CP-CNDS provides promising avenues for preventing and treating POPF, while exemplifying precision medicine-guided regulation of protein activity that effectively targets specific pathogenic molecules across multiple diseases.

Asunto(s)

Hidrogeles , Fístula Pancreática , Péptidos , Fístula Pancreática/prevención & control , Animales , Ratas , Hidrogeles/química , Masculino , Péptidos/farmacología , Péptidos/química , Péptidos/metabolismo , Quimotripsina/metabolismo , Complicaciones Posoperatorias/prevención & control , Tripsina/metabolismo , Tripsina/química , Lipasa/metabolismo , Humanos , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Páncreas/enzimología , Páncreas/patología

RESUMEN

The discovery of pancreatic lipase (PL) inhibitors is an essential route to develop new anti-obesity drugs. In this experiment, chitosan was used to add amino groups to cellulose filter paper (CFP) and then glutaraldehyde was used to covalently combine PL with amino-modified CFP through the Schiff base reaction. Under optimal immobilization conditions, CFP immobilized PL has a wide range of pH and temperature tolerance, as well as excellent reproducibility, reusability and storage stability. Subsequently, 26 natural products (NPs) were screened by immobilized PL with black tea extract having the highest inhibition rate. Three compounds with binding effects on PL (epigallocatechin gallate, theaflavin-3-gallate and theaflavin-3,3'-digallate) were captured. Molecular docking proved that these three compounds have a strong binding affinity for PL. Fluorescence spectra further revealed that theaflavin-3,3'-digallate could statically quench the intrinsic fluorescence of pancreatic lipase. The molecular docking and thermodynamic parameters indicated that electrostatic interaction was considered as the main interaction force between PL and theaflavin-3,3'-digallate. Finally, the potential anti-obesity targets and pathways of the three compounds were discussed through network pharmacology. This study not only proposes a simple and efficient method for screening PL inhibitors, but also sheds light on the anti-obesity mechanism of active compounds in black tea.

Asunto(s)

Fármacos Antiobesidad , Celulosa , Inhibidores Enzimáticos , Enzimas Inmovilizadas , Lipasa , Simulación del Acoplamiento Molecular , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Lipasa/química , Celulosa/química , Celulosa/análogos & derivados , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/antagonistas & inhibidores , Enzimas Inmovilizadas/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/química , Farmacología en Red , Páncreas/enzimología , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Catequina/metabolismo , Papel , Té/química , Evaluación Preclínica de Medicamentos

RESUMEN

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Asunto(s)

Curcuma , Curcumina , Diarilheptanoides , Inhibidores Enzimáticos , Lipasa , Simulación del Acoplamiento Molecular , Páncreas , Lipasa/antagonistas & inhibidores , Curcumina/farmacología , Curcumina/análogos & derivados , Curcumina/química , Curcuma/química , Diarilheptanoides/farmacología , Páncreas/enzimología , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Humanos , Plantas Medicinales/química

RESUMEN

This study examined the suppressive effects of 16 selected plant-based foods on α-glucosidase and pancreatic lipase and their antioxidant properties. Among these, the bark of Cinnamomum cassia (Cinnamon, WLN-FM 15) showed the highest inhibitory activity against α-glucosidase and the highest antioxidant activity. Additionally, WLN-FM 15 showed promising results in the other tests. To further identify the bioactive constituents of WLN-FM 15, a multi-bioactivity-labeled molecular networking approach was used through a combination of GNPS-based molecular networking, DPPH-HPLC, and affinity-based ultrafiltration-HPLC. A total of nine procyanidins were identified as antioxidants and inhibitors of α-glucosidase and pancreatic lipase in WLN-FM 15. Subsequently, procyanidins A1, A2, B1, and C1 were isolated, and their efficacy was confirmed through functional assays. In summary, WLN-FM 15 has the potential to serve as a functional food ingredient with the procyanidins as its bioactive constituents. These results also suggest that the multi-bioactivity-labeled molecular networking approach is reliable for identifying bioactive constituents in plant-based foods.

Asunto(s)

Antioxidantes , Biflavonoides , Catequina , Cinnamomum aromaticum , Inhibidores de Glicósido Hidrolasas , Lipasa , Corteza de la Planta , Proantocianidinas , Proantocianidinas/farmacología , Proantocianidinas/química , Proantocianidinas/análisis , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/análisis , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Corteza de la Planta/química , Cinnamomum aromaticum/química , Biflavonoides/farmacología , Biflavonoides/análisis , Biflavonoides/química , Catequina/análisis , Catequina/química , Catequina/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cromatografía Líquida de Alta Presión , Páncreas/enzimología , alfa-Glucosidasas/metabolismo , Farmacología en Red , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química

RESUMEN

Inhibition of pancreatic lipase (PL) is a strategy to prevent obesity. The inhibitory effects of Flos Sophorae Immaturus (FSI) extract and its main flavonoid components, rutin and quercetin, on PL were investigated. The contents of rutin and quercetin in FSI extract were 44.10 ± 1.33 % and 6.07 ± 1.62 %, respectively. The IC50 values of FSI extract, rutin and quercetin on PL were 322, 258 and 71 µg/mL, respectively. Rutin and quercetin inhibited PL in a reversible and noncompetitive manner. The combination of rutin and quercetin exhibited synergistic inhibitory effects at low concentration. The binding of rutin/quercetin with PL caused the fluorescence quenching of protein. Fluorescence titration showed the binding affinity of quercetin with PL protein was stronger than that of rutin. Circular dichroism analysis showed the binding changed the secondary structure of PL with an increase in random coil and a decrease in α-Helix and ß-Sheet. Molecular docking revealed that rutin and quercetin could interact with the amino acid residues around the catalytic site through multiple secondary interactions. In vivo studies showed that FSI extract can reduce fat absorption and promote fecal fat excretion through inhibition of PL activity, and the effects were mainly due to rutin and quercetin.

Asunto(s)

Flavonoides , Lipasa , Simulación del Acoplamiento Molecular , Páncreas , Extractos Vegetales , Quercetina , Rutina , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Lipasa/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Quercetina/farmacología , Quercetina/química , Páncreas/enzimología , Páncreas/efectos de los fármacos , Flavonoides/farmacología , Flavonoides/química , Rutina/farmacología , Rutina/química , Animales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Masculino , Sophora/química

RESUMEN

Background: Type 1 (T1D) and type 2 (T2D) diabetes lead to an aberrant metabolism of sialoglycoconjugates and elevated free serum sialic acid (FSSA) level. The present study evaluated sialidase and sialyltranferase activities in serum and some organs relevant to diabetes at early and late stages of T1D and T2D. Methods: Sialic acid level with sialidase and sialyltransferase activities were monitored in the serum, liver, pancreas, skeletal muscle and kidney of diabetic animals at early and late stages of the diseases. Results: The FSSA and activity of sialidase in the serum were significantly increased at late stage of both T1D and T2D while sialic acid level in the liver was significantly decreased in the early and late stages of T1D and T2D, respectively. Furthermore, the activity of sialidase was significantly elevated in most of the diabetes-relevant organs while the activity of sialyltransferase remained largely unchanged. A multiple regression analysis revealed the contribution of the liver to the FSSA while pancreas and kidney contributed to the activity of sialidase in the serum. Conclusions: We concluded that the release of hepatic sialic acid in addition to pancreatic and renal sialidase might (in)directly contribute to the increased FSSA during both types of diabetes mellitus.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Ácido N-Acetilneuramínico , Neuraminidasa , Sialiltransferasas , Animales , Neuraminidasa/metabolismo , Sialiltransferasas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ratas , Masculino , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/sangre , Hígado/metabolismo , Hígado/enzimología , Ratas Wistar , Páncreas/metabolismo , Páncreas/enzimología , Riñón/metabolismo , Músculo Esquelético/metabolismo

RESUMEN

BACKGROUND AND AIMS: To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals. METHODS: We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas. RESULTS: This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals. CONCLUSIONS: Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis.

Asunto(s)

Butirilcolinesterasa , Retroalimentación Fisiológica , Páncreas , Páncreas/enzimología , Perros , Humanos , Animales , Butirilcolinesterasa/metabolismo , Modelos Biológicos , Pancreatitis , Nervio Vago/fisiología

RESUMEN

Obesity has become a significant global health concern, affecting millions of people worldwide. One well-studied approach to identifying potential anti-obesity agents is the inhibition of pancreatic lipase (PL), an enzyme responsible for dietary fat digestion. This study investigated the inhibitory effects and mechanisms of galactolipid monogalactosyldiacylglycerol (MGDG), that was extracted from Brassica rapa ssp. chinensis on PL. Five different MGDG compounds were isolated and the results showed that compounds containing shorter fatty acid side chains and a higher degree of unsaturated bonds exhibit a greater inhibition effect on PL. Interestingly, both the kinetic study and the molecular docking prediction revealed a non-competitive inhibition of MGDG. Furthermore, the in vitro digestion model also showed that the consumption of MGDG extract with salad dressing was effective in delaying enzymatic fat digestion in a dose-dependent manner. These results suggest that MGDG from Brassica rapa ssp. chinensis may be a promising candidate for developing novel anti-obesity therapies.

Asunto(s)

Brassica rapa , Inhibidores Enzimáticos , Lipasa , Simulación del Acoplamiento Molecular , Páncreas , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Brassica rapa/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Páncreas/enzimología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Galactolípidos/química , Cinética , Digestión , Humanos

RESUMEN

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC50 < 1 µM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (Ki < 1 µM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo.

Asunto(s)

Inhibidores Enzimáticos , Flavanonas , Lipasa , Flavanonas/farmacología , Flavanonas/química , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Relación Estructura-Actividad , Humanos , Animales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Ratones , Simulación del Acoplamiento Molecular , Páncreas/enzimología , Páncreas/efectos de los fármacos , Masculino , Flavonoides/farmacología , Flavonoides/química , Descubrimiento de Drogas

RESUMEN

IMPORTANCE: Early diagnosis of canine pancreatitis is challenging due to non-specific clinical signs. Currently, abdominal ultrasonography and measurement of canine pancreatic lipase (cPL) have been employed for the diagnosis of pancreatitis. OBJECTIVE: Many qualitative and quantitative commercial cPL tests have been developed and used in veterinary clinics. This study aimed to compare three different methodologies SNAP cPL, Spec cPL, and Vcheck cPL tests to assess the concordance of these assays. METHODS: Fifty serum samples were collected from 36 dogs with or without pancreatitis and subjected to SNAP cPL, Spec cPL, and Vcheck cPL tests. Agreement and correlation coefficients were calculated between the test results, and correlations were determined during the management of the patients. RESULTS: The results of the three cPL assays were strongly correlated in 47/50 serum samples (94%). Cohen's kappa analysis between the Spec cPL and Vcheck cPL showed near perfect agreement (κ = 0.960, p < 0.001), SNAP cPL and Vcheck cPL (κ = 0.920, p < 0.001), and Spec cPL and SNAP cPL (κ = 0.880, p < 0.001). The correlation coefficients (r) between data from Spec cPL and Vcheck cPL tests was calculated by Spearman's correlation test (r = 0.958, p < 0.001). Furthermore, the patterns of change in serum cPL concentrations determined using Spec cPL and Vcheck cPL were significantly consistent during the monitoring period in 11 patients. CONCLUSIONS AND RELEVANCE: Our data illustrated that Spec cPL and Vcheck cPL tests are compatible for clinical use in the diagnosis and monitoring of canine pancreatitis.

Asunto(s)

Enfermedades de los Perros , Lipasa , Pancreatitis , Animales , Perros , Lipasa/sangre , Pancreatitis/veterinaria , Pancreatitis/diagnóstico , Pancreatitis/sangre , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/sangre , Masculino , Femenino , Páncreas/enzimología

RESUMEN

Triacylglycerols (TAGs) are a primary energy source for marine mammals during lipid digestion. Walruses (Odobenus rosmarus divergens) consume prey with a high content of long-chain polyunsaturated fatty acids; however, their digestive physiology and lipid digestion remain poorly studied. The present study aims to model and characterize the gastric (PWGL) and pancreatic (PWPL) lipases of Pacific walruses using an in-silico approach. The confident 3D models of PWGL and PWPL were obtained via homology modeling and protein threading and displayed the structural features of lipases. Molecular docking analysis demonstrated substrate selectivity for long-chain TAG (Trieicosapentaenoin; TC20:5n-3) in PWGL and short-chain TAG (Trioctanoin; TC8:0) in PWPL. Molecular dynamics simulations demonstrate that PWGL bound to tridocosahexaenoin (TC22:6n-3), the protein is considerably stable at all three salinity conditions, but fluctuations are observed in the regions associated with catalytic sites and the lid, indicating the potential hydrolysis of the substrate. This is the first study to report on the digestion of TAGs in walruses, including modeling and lipases characterization and proposing a digestive tract for pinnipeds.

Asunto(s)

Lipasa , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Páncreas , Animales , Lipasa/metabolismo , Lipasa/química , Páncreas/enzimología , Morsas/metabolismo , Metabolismo de los Lípidos , Especificidad por Sustrato , Triglicéridos/metabolismo , Digestión , Estómago/enzimología , Secuencia de Aminoácidos

Asunto(s)

Virus de la Hepatitis E , Hepatitis E , Hepatitis E/transmisión , Hepatitis E/tratamiento farmacológico , Animales , Humanos , Porcinos , Páncreas/enzimología

RESUMEN

OBJECTIVE: Assess markers for pancreatic function and gastrointestinal malabsorption in African painted dogs (Lycaon pictus), including canine trypsin-like immunoreactivity (cTLI), canine pancreatic lipase immunoreactivity (cPLI), cobalamin, and folate at one North American facility. ANIMALS: 15 healthy African painted dogs held at one institution were sampled during routine health examinations. METHODS: Blood was collected at routine health examinations, and serum was separated and stored until testing. Serum was analyzed for cTLI, cPLI, cobalamin, and folate. The results were evaluated for correlation to sex, age, and storage time of samples. RESULTS: All individuals had cTLI and folate levels below normal reference ranges for domestic dogs (< 5.0 µg/L and < 7.7 µg/L, respectively). Cobalamin values were within or above reported domestic dog ranges, and cPLI values were within range as well. No analytes were significantly influenced by sex or time in storage, while cTLI was positively correlated with age. CLINICAL RELEVANCE: cTLI and folate did not fall within normal domestic canid reference ranges in this population of healthy African painted dogs. Clinical interpretation of these values based on domestic canid recommendations would indicate clinical disease, which was not apparent in this population. Analytes for pancreatic function and malabsorption or gastrointestinal indicators, including cTLI, cPLI, and folate, in African painted dogs should be interpreted with caution when using domestic dog references ranges.

Asunto(s)

Animales de Zoológico , Ácido Fólico , Lipasa , Vitamina B 12 , Animales , Masculino , Lipasa/sangre , Lipasa/metabolismo , Femenino , Vitamina B 12/sangre , Ácido Fólico/sangre , Canidae , Valores de Referencia , Tripsina/metabolismo , Tripsina/sangre , Páncreas/enzimología

RESUMEN

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the ß-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.

Asunto(s)

Apigenina , Inhibidores Enzimáticos , Lipasa , Páncreas , Espectrometría de Fluorescencia , Animales , Apigenina/química , Apigenina/farmacología , Dicroismo Circular , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Lipasa/antagonistas & inhibidores , Lipasa/metabolismo , Lipasa/química , Páncreas/enzimología

RESUMEN

The purpose of this review was to analyze the scientific literature on exocrine pancreatic insufficiency (EPI) in dogs and cats and our own research on porcine model to compare animal- and microbial-derived enzymes in the treatment of animals with this disease. Clinical signs of EPI occur when more than 85% of the pancreatic parenchyma is non-functional. EPI can be a consequence of various diseases. The insufficient activity or deficiency of pancreatic enzymes leads to impaired digestion and absorption, and consequently, to malnutrition. The primary treatment for enzyme insufficiency is pancreatic enzyme replacement therapy (PERT). PERT in animals with EPI is a lifetime therapy. Most commercially available products are of animal origin (processed pancreata obtained from a slaughter house) and contain lipases, alpha-amylase, and proteases. Enzymes of microbial and plant origin seem to be a promising alternative to animal-derived enzymes, but to date there are no registered preparations containing all enzymes simultaneously for use in clinical practice to treat EPI. Results from some previous studies have highlighted the "extra-digestive" functions of pancreatic enzymes, as well as the actions of pancreatic-like microbial enzymes. For example, trypsin activates protease-activated receptor and provokes maturation of enterocytes and enterostatin inhibits fat absorption. It has been postulated that intrapancreatic amylase is the main component of the acini-islet-acinar axis-the reflex which down regulates insulin release, while gut and blood amylase exhibit anti-incretin actions "per se." Additionally, high but still physiological blood amylase activity coincide with physiological glucose homeostasis and a lack of obesity.

Asunto(s)

Enfermedades de los Gatos , Enfermedades de los Perros , Terapia de Reemplazo Enzimático , Insuficiencia Pancreática Exocrina , Animales , Insuficiencia Pancreática Exocrina/veterinaria , Insuficiencia Pancreática Exocrina/tratamiento farmacológico , Insuficiencia Pancreática Exocrina/enzimología , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/enzimología , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/enzimología , Perros , Terapia de Reemplazo Enzimático/veterinaria , Gatos , Porcinos , Páncreas/enzimología , Lipasa/metabolismo

RESUMEN

Our prior results showed that an acute bout of endurance exercise for 6 h, but not 1 h, decreased pancreatic amylase activity, indicating that acute endurance exercise may affect carbohydrate digestive capacity in an exercise duration-dependent manner. Here, we investigated the effects of acute endurance exercise of different intensities on mouse pancreatic amylase activity. Male C57BL/6J mice performed low- or high-intensity running exercise for 60 min at either 10 (Ex-Low group) or 20 m/min (Ex-High group). The control group comprised sedentary mice. Immediately after acute exercise, pancreatic amylase activity was significantly decreased in the Ex-High group and not the Ex-Low group in comparison with the control group. To determine whether the decreased amylase activity induced by high-intensity exercise influenced muscle glycogen recovery after exercise, we investigated the rates of muscle glycogen resynthesis in Ex-High group mice administered either oral glucose or starch solution (2.0 mg/g body weight) immediately after exercise. The starch-fed mice exhibited significantly lower post-exercise glycogen accumulation rates in the 2-h recovery period compared with the glucose-fed mice. This difference in the glycogen accumulation rate was absent for starch- and glucose-fed mice in the sedentary (no exercise) control group. Furthermore, the plasma glucose AUC during early post-exercise recovery (0-60 min) was significantly lower in the starch-fed mice than in the glucose-fed mice. Thus, our findings suggest that acute endurance exercise diminishes the carbohydrate digestive capacity of the pancreas in a manner dependent on exercise intensity, with polysaccharides leading to delayed muscle glycogen recovery after exercise.

Asunto(s)

Glucógeno , Ratones Endogámicos C57BL , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Masculino , Glucógeno/metabolismo , Condicionamiento Físico Animal/fisiología , Músculo Esquelético/metabolismo , Amilasas/metabolismo , Ratones , Glucemia/metabolismo , Almidón/metabolismo , Glucosa/metabolismo , Resistencia Física/fisiología , Carrera/fisiología , Páncreas/enzimología , Páncreas/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/metabolismo

RESUMEN

BACKGROUND: It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. HYPOTHESIS/OBJECTIVES: Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. ANIMALS: 51 client-owned dogs with signs of gastrointestinal disease. METHODS: Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). RESULTS: Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 µg/L; P < 0.001) and 4 hours (29.6 ± 13.1 µg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 µg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 µg/L) was equivalent to baseline (13.7 ± 8.3 µg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

Asunto(s)

Enfermedades de los Perros , Ácido Fólico , Enfermedades Gastrointestinales , Lipasa , Vitamina B 12 , Animales , Perros , Enfermedades de los Perros/sangre , Enfermedades de los Perros/diagnóstico , Ácido Fólico/sangre , Vitamina B 12/sangre , Masculino , Lipasa/sangre , Femenino , Enfermedades Gastrointestinales/veterinaria , Enfermedades Gastrointestinales/sangre , Estudios Prospectivos , Enfermedad Crónica/veterinaria , Periodo Posprandial , Tripsina/sangre , Páncreas/enzimología