RESUMEN
Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps.
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Páncreas Exocrino , Pancreatitis , Humanos , Pancreatitis/fisiopatología , Pancreatitis/complicaciones , Páncreas Exocrino/fisiopatología , Insuficiencia Pancreática Exocrina/fisiopatología , Insuficiencia Pancreática Exocrina/etiología , Enfermedad AgudaRESUMEN
BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.
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Hiperlipidemias , Pancreatitis Crónica , Humanos , Ácido 4-Aminobenzoico , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico por imagen , Páncreas , Pruebas de Función Pancreática , ColesterolRESUMEN
BACKGROUND AND AIM: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). METHODS: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods. RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. CONCLUSIONS: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis.
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Apolipoproteína A-II , Insuficiencia Pancreática Exocrina , Pancreatitis Crónica , Humanos , Ácido 4-Aminobenzoico , Apolipoproteína A-II/metabolismo , Insuficiencia Pancreática Exocrina/complicaciones , Pruebas de Función Pancreática/métodos , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico por imagen , Isoformas de Proteínas/análisisRESUMEN
Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.
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Insuficiencia Pancreática Exocrina/diagnóstico , Heces/enzimología , Elastasa Pancreática/metabolismo , Pruebas de Función Pancreática/métodos , Esteatorrea/diagnóstico , Biomarcadores/metabolismo , Terapia de Reemplazo Enzimático , Insuficiencia Pancreática Exocrina/sangre , Humanos , Desnutrición , Índice de Severidad de la Enfermedad , Esteatorrea/sangre , Vitaminas/sangreRESUMEN
BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.
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Adenoma , Neoplasias Colorrectales , Enfermedad del Hígado Graso no Alcohólico , Adenoma/epidemiología , Adenoma/etiología , Amilasas , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Estudios Transversales , Humanos , Enfermedad del Hígado Graso no Alcohólico/etiología , Factores de RiesgoRESUMEN
PURPOSE: Laparoscopic duodenum-preserving pancreatic head resection (L-DPPHR) is technically demanding with extreme difficulty in biliary preservation. Only a few reports of L-DPPHR are available with alarming bile leakage, and none of them revealed the long-term metabolic outcomes. For the first time, our study explored the different dosage and timing of indocyanine green (ICG) for guiding L-DPPHR and described the long-term metabolic results. METHODS: Between October 2015 and January 2021, different dosage and timing of ICG were administrated preoperatively and evaluated intra-operatively using Image J software to calculate the relative fluorescence intensity ratio of signal-to-noise contrast between bile duct and pancreas. Short-term complications and long-term metabolic disorder were collected in a prospectively maintained database and analyzed retrospectively. RESULTS: Twenty-five patients were enrolled without conversion to laparotomy or pancreaticoduodenectomy. Administrating a dosage of 0.5 mg/kg 24 h before the operation had the highest relative fluorescence intensity ratio of 19.3, and it proved to guide the biliary tract the best. Fifty-six percent of patients suffered from postoperative complications with 48% experiencing pancreatic fistula and 4% having bile leakage. No one suffered from the duodenal necrosis, and there was no mortality. When compared with the non-ICG group, the ICG group had a comparable diameter of tumor and similar safety distance from lesions to common bile duct; however, it decreased the incidence of bile leakage from 10% to none. The median length of hospital stay was 16 days. After a median follow-up of 26.6 months, no one had tumor recurrence or refractory cholangitis. No postoperative new onset of diabetes mellitus (pNODM) was observed, while pancreatic exocrine insufficiency (pPEI) and non-alcoholic fatty liver disease (NAFLD) were seen in 4% of patients 12 months after the L-DPPHR. CONCLUSION: L-DPPHR is feasible and safe in selected patients, and real-time ICG imaging with proper dosage and timing may greatly facilitate the identification and the prevention of biliary injury. And it seemed to be oncological equivalent to PD with preservation of metabolic function without refractory cholangitis.
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Colangitis , Laparoscopía , Neoplasias Pancreáticas , Humanos , Verde de Indocianina , Estudios Retrospectivos , Duodeno/cirugía , Pancreatectomía/métodos , Pancreaticoduodenectomía/métodos , Conducto Colédoco/cirugía , Laparoscopía/efectos adversos , Morbilidad , Neoplasias Pancreáticas/cirugíaRESUMEN
Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.
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Envejecimiento/genética , Páncreas/metabolismo , Péptidos/genética , Proteómica , Envejecimiento/patología , Secuencia de Aminoácidos/genética , Animales , Cromatografía Liquida , Diabetes Mellitus/genética , Diabetes Mellitus/patología , Humanos , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Ratones , Páncreas/patología , Péptidos/aislamiento & purificación , Espectrometría de Masas en TándemRESUMEN
The microbiota living in gut influence the immune response, metabolism, mood and behavior. The diet plays a pivotal role in maintaining healthy gut microbiota composition and its fermentation leads to production of Short Chain Fatty Acids (SCFAs) mainly acetate, propionate and butyrate. During pancreatic dysfunction, insulin mediated suppression of glucagon is impaired leading to uncontrolled glucose production by liver and state of hyperglycemia. Insulin and glucagon balance is as important as insulin sensitivity which is reduced during Type 2 Diabetes (T2D). Glucagon like peptide-1 (GLP1) produced by Intestinal epithelial cells regulates insulin and glucagon secretion directly via GLP1 receptor on pancreatic cells or via nervous system. But half-life period of GLP1 is very short i.e. about 2â¯min, after which it is cleaved and inactivated. SCFAs are well documented to induce GLP1 but its direct effect on pancreatic dysfunction has not been reported. This review opens a new avenue to study the role of SCFAs as treatment to pancreatic dysfunction and T2D.
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Diabetes Mellitus Tipo 2/complicaciones , Ácidos Grasos Volátiles/biosíntesis , Microbioma Gastrointestinal/fisiología , Enfermedades Pancreáticas/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Humanos , Enfermedades Pancreáticas/metabolismoRESUMEN
Background & objectives: Diabetes mellitus (DM) is an important risk factor for tuberculosis and has received increasing emphasis. However, the reverse association of tuberculosis impacting blood sugar levels has not been well studied. The present study was conducted to evaluate the prevalence of hyperglycemia in patients with tuberculosis and assess its resolution following successful treatment of tuberculosis. Methods: In this prospective study, a total of 582 patients with tuberculosis were evaluated for hyperglycaemia [DM or impaired glucose tolerance (IGT)] with random blood sugar (RBS) and all patients with RBS >100 mg/dl were subjected to a 75 g oral glucose tolerance test (OGTT). All patients received thrice weekly intermittent Directly Observed Treatment Short Course (DOTS) for tuberculosis. Patients with hyperglycaemia were re-evaluated at the end of anti-tuberculosis treatment with an OGTT and glycated hemoglobin (HbA1c) levels to assess for glycaemic status. Results: In the present study, 41 of the 582 patients were found to have DM [7%, 95% confidence interval (CI) (5.2, 9.4)] while 26 patients were found to have IGT [4.5%, 95% CI (3, 6.5)]. Three patients were lost to follow up. Of the 26 patients with IGT, 17 [65.4%, 95% CI (46.1, 80.7)] reverted to euglycaemic status following successful treatment of tuberculosis, while the blood sugar levels improved in all patients with DM following treatment of tuberculosis. Interpretation & conclusions: Our study results show that tuberculosis adversely impacts glycaemic status with improvement in blood sugar levels at the end of successful treatment of tuberculosis. Longitudinal studies with large sample size are required to confirm these findings.
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Diabetes Mellitus Tipo 2/epidemiología , Hiperglucemia/epidemiología , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Glucemia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Humanos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tuberculosis/sangre , Tuberculosis/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Chronic pancreatic dysfunction is frequently observed as a consequence of prolonged high-fat diet consumption and is a serious public health concern. This pro-diabetic insult aggravates inflammation-influenced fibrotic lesions and is associated with deregulated autophagy. Metformin, a conventional anti-hyperglycemic drug, might be beneficial for pancreatic health, but the complex molecular regulations are not clarified. Considering the worldwide prevalence of chronic pancreatic dysfunction in obese individuals, we aimed to unwind the molecular intricacies explaining the involvement of oxidative stress, inflammation and fibrosis and to approbate metformin as a plausible intervention in this crossroad. MAIN METHODS: Age-matched Swiss Albino mice were exposed to high-fat diet (60 kcal%) against control diet (10 kcal%) to establish diet-induced stress model. Metformin treatment was introduced after 4 weeks to metformin-control and HFD-exposed metformin groups. After 8 weeks, metabolic and molecular outcomes were assessed to establish the impact of metformin on chronic consequences of HFD-mediated injury. KEY FINDINGS: High-fat diet administration to healthy mice primes oxidative stress-mediated chronic inflammation through Nrf2/Keap1/NF-κB interplay. Besides, pro-inflammatory cytokine bias leading to fibrotic (increased TGF-ß, α-SMA, and MMP9) and pro-EMT (Twist1, Slug, Vimentin, E-cadherin) repercussions in pancreatic lobules were evident. Metformin distinctly rescues high-fat diet-induced remodeling of pancreatic pro-diabetic alterations and cellular survival/death switch. Further, metformin abrogates the p62-Twist1 crosstalk in an autophagy-dependent manner (elevated beclin1, LC3-II/I, Lamp2) to restore pancreatic homeostasis. CONCLUSION: Our research validates the therapeutic potential of metformin in the inflammation-fibrosis nexus to ameliorate high-fat diet-induced pancreatic dysfunction and related metabolic alterations.
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Autofagia , Dieta Alta en Grasa , Fibrosis , Metformina , Estrés Oxidativo , Animales , Metformina/farmacología , Dieta Alta en Grasa/efectos adversos , Autofagia/efectos de los fármacos , Ratones , Estrés Oxidativo/efectos de los fármacos , Masculino , Transición Epitelial-Mesenquimal/efectos de los fármacos , Inflamación/patología , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Páncreas/patología , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismoRESUMEN
Acacetin is a natural flavonoid compound with multiple therapeutic potential in oxidative stress, inflammation, cancers, cardiovascular disease and infections. The present study aimed to detect the effect of acacetin on pancreatic and hepatorenal dysfunction in type 2 diabetic rats. The diabetic rats were induced by high-fat diet (HFD) followed by intraperitoneal injection of streptozotocin (STZ) at a dose of 45 mg/kg. Different doses of acacetin were orally administrated once a day for 8 weeks after the diabetic model was successfully established. The experimental results revealed that acacetin and acarbose displayed obvious attenuation in the levels of fasting blood glucose (FBG) and lipids compared to the untreated diabetic rats. In addition, the physiological function of liver and kidney was impaired in the persistent environment of hyperglycemia, while acacetin improved the damage of liver and kidney. Furthermore, hematoxylin-eosin (H&E) staining indicated that acacetin alleviated the pathological alterations of the pancreas, liver and kidney tissues. Besides, the increased levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8 and malondialdehyde (MDA) were recused by acacetin treatment, while the reduction of superoxide dismutase (SOD) levels were suppressed by acacetin treatment. In conclusion, the experimental results demonstrated that acacetin improved the lipids and glucose levels, and hepatorenal antioxidant capacity, as well as ameliorated hepatorenal dysfunction in type 2 diabetic rats, and the potential mechanism might be associated with its antioxidant and anti-inflammatory activities.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratas , Animales , Antioxidantes/farmacología , Estreptozocina/toxicidad , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Dieta Alta en Grasa/efectos adversos , Glucemia , Páncreas , Estrés Oxidativo , Diabetes Mellitus Tipo 2/patología , Hígado , LípidosRESUMEN
OBJECTIVE: Insulinomas are rare in the post-bariatric surgery setting. The differential diagnosis for hypoglycemia is broad, requiring laboratory testing to verify endogenous hyperinsulinemic hypoglycemia. Selective arterial calcium stimulation testing (SACST) can help localize abnormal insulin production. We describe a patient with histologically confirmed insulinoma after bariatric surgery diagnosed with the aid of SACST. METHODS: We present a 67 year old woman with a history of Roux-en-Y bypass surgery who presented with endogenous hyperinsulinemic hypoglycemia. Initially, no pancreatic lesion was identified radiologically. We pursued SACST to localize the source of insulin production. RESULTS: The SACST successfully localized the source of hyperfunctioning islet cells to the pancreatic tail with absolute insulin values in a range consistent with insulinoma. Additional radiologic studies showed a small tumor in the pancreatic tail. Pathology showed a well-differentiated neuroendocrine tumor, compatible with insulinoma. CONCLUSION: This case study illustrates the usefulness of SACST for the diagnosis and localization of insulinoma.
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Cirugía Bariátrica , Hiperinsulinismo , Insulinoma , Neoplasias Pancreáticas , Anciano , Calcio , Femenino , Humanos , Insulinoma/diagnóstico , Insulinoma/patología , Insulinoma/cirugía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugíaRESUMEN
Although the pathophysiological mechanisms and consequences of gross derangements in iron metabolism are well known, little is known about the pathophysiological mechanisms underlying mild-to-moderate alterations in iron metabolism and their consequences. Growing evidence indicates that the exocrine pancreas has a bidirectional relationship with iron metabolism. Studies have shown alterations in circulating markers of iron metabolism, iron absorption, and intra-pancreatic iron deposition in pancreatitis. At the same time, exocrine pancreatic dysfunction has been shown in iron overload disorders. These observations reveal a compelling connection between the exocrine pancreas and iron metabolism, which are further elucidated by observations of therapeutic benefits of iron chelating agents and pancreatic enzyme replacement therapy. While the pancreas is not a major reservoir of iron in the body, better understanding of its relationship with iron metabolism may yield unexpected insights.
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Páncreas Exocrino , Pancreatitis , Humanos , Hierro , PáncreasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has traditionally been used as a medicinal herb to treat stress, anxiety, and insomnia. Current reports suggest that not only chronic stress stimulates angiogenesis, but angiogenesis also regulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from Melissa officinalis inhibits angiogenesis, we hypothesized that ALS-L1023 could suppress visceral obesity and insulin resistance in obese female C57BL/6J mice, a mouse model of obese premenopausal women. MATERIALS AND METHODS: The mice were grouped and fed for 16 weeks as follows: 1) low-fat diet (LFD), 2) high-fat diet (HFD), or 3) HFD supplemented with 0.4 or 0.8% ALS-L1023. Variables and determinants of visceral obesity, insulin resistance, and pancreatic dysfunction were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: ALS-L1023 decreased weight gain, visceral adipocyte size, and serum lipid levels in HFD-fed obese mice. ALS-L1023 also normalized hyperglycemia and hyperinsulinemia and concomitantly reduced blood glucose levels during oral glucose tolerance tests. The pancreatic islet size and insulin-positive ß-cell area were significantly reduced in ALS-L1023-treated mice compared with untreated obese controls, reaching a level similar to that of LFD-fed lean mice. ALS-L1023 suppressed pancreatic lipid accumulation, infiltration of inflammatory cells, and collagen levels. ALS-L1023 treatment altered the pancreatic expression of genes involved in steatosis, inflammation, and fibrosis. CONCLUSIONS: Our findings indicate that the herbal extract ALS-L1023 from Melissa officinalis not only inhibits visceral obesity, but also attenuates the increased fasting blood glucose, impaired glucose tolerance, and pancreatic dysfunction seen in female obese mice. These results suggest that ALS-L1023 may be effective in the prevention of visceral obesity and insulin resistance in obese premenopausal women.
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Fármacos Antiobesidad/uso terapéutico , Melissa , Obesidad Abdominal/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Adipocitos/efectos de los fármacos , Adipocitos/patología , Animales , Glucemia/análisis , Ácidos Grasos no Esterificados/sangre , Femenino , Fibrosis , Resistencia a la Insulina , Ratones Endogámicos C57BL , Obesidad Abdominal/sangre , Obesidad Abdominal/patología , Páncreas/efectos de los fármacos , Páncreas/patología , Triglicéridos/sangreRESUMEN
It has been well established that glucotoxicity induces pancreatic ß-cells dysfunction; however, the precise mechanism remains unclear. Our previous studies demonstrated that high glucose concentrations are associated with decreased hepcidin expression, which inhibits insulin synthesis. In this study, we focused on the role of low hepcidin level-induced increased iron deposition in ß-cells and the relationship between abnormal iron metabolism and ß-cell dysfunction. Decreased hepcidin expression increased iron absorption by upregulating transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) expression, resulting in iron accumulation within cells. Prussia blue stain and calcein-AM assays revealed greater iron accumulation in the cytoplasm of pancreatic tissue isolated from db/db mice, cultured islets and Min6 cells in response to high glucose stimulation. Increased cytosolic iron deposition was associated with greater Fe2+ influx into the mitochondria, which depolarized the mitochondria membrane potential, inhibited ATP synthesis, generated excessive ROS and induced oxidative stress. The toxic effect of excessive iron on mitochondrial function eventually resulted in impaired insulin secretion. The restricted iron content in db/db mice via reduced iron intake or accelerated iron clearance improved blood glucose levels with decreased fasting blood glucose (FBG), fasting blood insulin (FIns), HbA1c level, as well as improved intraperitoneal glucose tolerance test (IPGTT) results. Thus, our study may reveal the mechanism involved in the role of hepcidin in the glucotoxcity impaired pancreatic ß cell function pathway.
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Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome classically associated with exocrine pancreatic dysfunction and neutropenia, with a predisposition toward progressive marrow failure, risk of myelodysplastic syndrome, and leukemia. Most patients carry biallelic mutations in the Shwachman-Bodian-Diamond Syndrome gene, which is an integral component of ribosome maturation and biogenesis. This article reviews the diagnosis, clinical characteristics, and treatment modalities of SDS, and reports advances in the understanding of the molecular pathophysiology of SDS.
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Enfermedades de la Médula Ósea , Insuficiencia Pancreática Exocrina , Lipomatosis , Enfermedades de la Médula Ósea/diagnóstico , Enfermedades de la Médula Ósea/genética , Enfermedades de la Médula Ósea/patología , Enfermedades de la Médula Ósea/terapia , Insuficiencia Pancreática Exocrina/diagnóstico , Insuficiencia Pancreática Exocrina/genética , Insuficiencia Pancreática Exocrina/patología , Insuficiencia Pancreática Exocrina/terapia , Pruebas Genéticas , Humanos , Lipomatosis/diagnóstico , Lipomatosis/genética , Lipomatosis/patología , Lipomatosis/terapia , Patología Molecular , Síndrome de Shwachman-DiamondRESUMEN
Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 µmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 µmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 µmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy. Based on our data, we suggest that TBI is detrimental for pancreatic functions, and speculate that DFO may contribute to the rapid pancreatic IO observed in these patients.
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BACKGROUND: Acute pancreatitis is one of the most common causes of gastrointestinal-related hospitalization and the incidence is increasing. Endo- and exocrine pancreatic function can be compromised after acute pancreatitis. OBJECTIVE: The purpose of this study was to explore the long-term consequences of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) on pancreatic function. METHODS: A follow-up study was carried out with prospective assessment of endo- and exocrine pancreatic function among cases with previous PEP and matched controls from a Danish cohort consisting of 772 patients undergoing first-time ERCP. Pancreatic function was evaluated by faecal-elastase-1 test, blood levels of haemoglobin A1c, C-peptide, vitamin B12, vitamin D and indirectly by changes in body weight. RESULTS: Twenty-nine cases and 49 controls participated in the study. Mean follow-up time (standard deviation) was 58 (21) months. Twelve (41%), eight (28%) and nine (31%) patients had mild, moderate and severe PEP, respectively. There was no difference between cases and controls with regard to pancreatic function parameters and PEP severity was not associated with pancreatic function. Factors associated with pancreatic function impairment included body mass index, alcohol consumption, age and smoking. CONCLUSION: This study suggests that long-term pancreatic function following PEP is similar to the pancreatic function of other patients with comparable gallstone-related morbidity.
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Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder of marrow failure syndrome and exocrine pancreatic dysfunction with an estimated incidence of 1/76,000. When present, characteristic skeletal abnormalities are strongly suggestive of SDS but most often they are seen during childhood and adolescence. We present a case of preterm twins with prenatal diagnosis of thoracic hypoplasia and a clinical evolution that lead to an early diagnosis of SDS. This report highlights the importance of a high index of suspicion for SDS in case of neonatal thoracic hypoplasia.