Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.

The Effect of Tuberculosis Infection on Pancreatic Beta-Cell Function in Patients with Type 2 Diabetes Mellitus

Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.

Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis

BACKGROUND Type 2 diabetes mellitus(T2DM)has been shown to be correlated with hepatocellular carcinoma(HCC)development.However,further investigation is needed to understand how T2DM characteristics affect the prognosis of chronic hepatitis B(CHB)patients.AIM To assess the effect of T2DM on CHB patients with cirrhosis and to determine the risk factors for HCC development.METHODS Among the 412 CHB patients with cirrhosis enrolled in this study,there were 196with T2DM.The patients in the T2DM group were compared to the remaining 216patients without T2DM(non-T2DM group).Clinical characteristics and outcomes of the two groups were reviewed and compared.RESULTS T2DM was significantly related to hepatocarcinogenesis in this study(P=0.002).The presence of T2DM,being male,alcohol abuse status,alpha-fetoprotein>20ng/mL,and hepatitis B surface antigen>2.0 log IU/mL were identified to be risk factors for HCC development in the multivariate analysis.T2DM duration of more than 5 years and treatment with diet control or insulin±sulfonylurea significantly increased the risk of hepatocarcinogenesis.CONCLUSION T2DM and its characteristics increase the risk of HCC in CHB patients with cirrhosis.The importance of diabetic control should be emphasized for these patients.

Diabetes mellitus as a consequence of acute severe pancreatitis:Unraveling the mystery

The occurrence of diabetes mellitus(DM)in pancreatitis is being increasingly recognized lately.Diabetes can develop not only with chronic pancreatitis but even after the first episode of acute pancreatitis(AP).The incidence of diabetes after AP varies from 18%to 23%in 3 years and reaches up to 40%over 5 years.The exact pathogenesis of diabetes after AP is poorly understood and various mechanisms proposed include loss of islet cell mass,AP-induced autoimmunity,and alterations in the insulin incretin axis.Risk factors associated with increased risk of diabetes includes male sex,recurrent attacks of pancreatitis,presence of pancreatic exocrine insufficiency and level of pancreatitic necrosis.Diagnosis of post-pancreatitis DM(PPDM)is often excluded.Treatment includes a trial of oral antidiabetic drugs in mild diabetes.Often,insulin is required in uncontrolled diabetes.Given the lack of awareness of this metabolic disorder after AP,this review will evaluate current information on epidemiology,risk factors,diagnosis and management of PPDM and identify the knowledge gaps.

Diagnosis and treatment of diabetes mellitus in chronic pancreatitis

Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus.It is a clinically relevant condition with a prevalence of 5%-10%among all diabetic subjects in Western populations.In nearly 80%of all type 3c diabetes mellitus cases,chronic pancreatitis seems to be the underlying disease.The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far.In contrast to the management of type 1 or type2 diabetes mellitus,the endocrinopathy in type 3c is very complex.The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition.General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus(up to 90%of all cases)is rather good.However,in a patient first presenting with diabetes mellitus,chronic pancreatitis as a potential causative condition is seldom considered.Thus many patients are misdiagnosed.The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy.In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency,preventing or treating a lack of fat-soluble vitamins(especially vitamin D)and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

AIM: To evaluate the utility of carbohydrate antigen19-9(CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis.METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis.Pooled analysis was performed using random-effects models, and receiver operating characteristic(ROC) curves were generated.Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools.RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included.Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81(95%CI: 0.80-0.83); specificity, 0.81(95%CI: 0.79-0.82); positive likelihood ratio, 4.08(95%CI: 3.39-4.91); negative likelihood ratio, 0.24(95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31(95%CI: 14.40-25.90).The area under the ROC curve was 0.88.No significant publication bias was detected.CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy.

Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

AIM:To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis(AP).METHODS:Patients with AP were invited to participate in the study.Severity of AP was determined by the Atlanta classification and definitions revised in2012.Pancreatic exocrine insufficiency(PEI)was diagnosed by the concentration of fecal elastase-1.An additional work-up,including laboratory testing of serum nutritional markers for determination ofmalnutrition,was offered to all patients with low levels of fecal elastase-1 FE.Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus,and type 3c diabetes mellitus(T3c DM)was diagnosed according to American Diabetes Association criteria.RESULTS:One hundred patients were included in the study:75%(75/100)of patients had one attack of AP and 25%(25/100)had two or more attacks.The most common etiology was alcohol.Mild,moderately severe and severe AP were present in 67,15 and 18%of patients,respectively.The mean time from attack of AP to inclusion in the study was 2.7 years.PEI was diagnosed in 21%(21/100)of patients and T3c DM in14%(14/100)of patients.In all patients with PEI,at least one serologic nutritional marker was below the lower limit of normal.T3c DM was more frequently present in patients with severe AP(P=0.031),but was also present in some patients with mild and moderately severe AP.PEI was present in all degrees of severity of AP.There were no statistically significantly differences according to gender,etiology and number of AP attacks.CONCLUSION:As exocrine and endocrine pancreatic insufficiency can develop after AP,routine follow-up of patients is necessary,for which serum nutritional panel measurements can be useful.

Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging

AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis.CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.

Post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition as harbingers of pancreatic cancer

Progress in the fight against pancreatic cancer has been hampered by many factors.One of them is the inability to detect the disease early in overwhelming majority of patients.The present paper outlines a novel way in which progress could be accelerated.This includes a focus on two harbingers—post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition—that converge at affecting the tumor macroenvironment and microenvironment specifically in the pancreas,not other organs.The two entities have the potential to be incorporated into future screening strategies with a view to early detecting of pancreatic cancer.

Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with diabetes mellitus

The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk factor for acute pancreatitis and approximately 2% to 5% of cases of acute pancreatitis are related to drugs. We report on tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 40 years old woman with type 2 diabetes mellitus occurred by dexamethasone. She was treated with insulin infusion and fenofibrate, and goserelin acetate was started instead of tamoxifen after discharge from the hospital. Also, probable pathogenic hypotheses about the correlation between tamoxifen and dexamethasone induced type 2 diabetes mellitus on severe acute pancreatitis are provided. Clinicians should take care of risks of severe acute pancreatitis on using tamoxifen, especially for patients with dexamethasone induced diabetes mellitus. These individuals should undergo pre-post tamoxifen lipid screening and careful history taking of drugs, including dexamethasone.

Pancreatic steatosis: Is it related to either obesity or diabetes mellitus?

The accumulation of fat in the pancreatic gland has been referred to using various synonyms,such as pancreatic lipomatosis,fatty replacement,fatty infiltration,fatty pancreas,lipomatous pseudohypertrophy,non-alcoholic fatty pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis is the best description of fat accumulation in the pancreatic gland without fat replacement,and this term also describes the possibility that the fat accumulation is a reversible process.A review of the existing literature was carried out,and it was found that there was notable evidence from both the pathological and the imaging point of view that pancreatic steatosis is an increasing problem due to the increasing incidence of obesity.The conclusion was that pancreatic steatosis was easily detectable using modern imaging techniques,such as ultrasonography,endoscopic ultrasonography,computed tomography and magnetic resonance imaging.Pancreatic steatosis was not due to the presence of diabetes mellitus but was highly associated with the metabolic syndrome.The possible presence of steatopancreatitis should be better evaluated,especially regarding the inflammatory cascade,and additional studies are needed which are capable of assessing whether non-alcoholic steatopancreatitis really exists as does non-alcoholic steatohepatitis.Finally,the presence of exocrine pancreatic function should be extensively evaluated in patients with pancreatic steatosis.

Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma:a cross-sectional case-control study from Chinese patients with HBV infection

BACKGROUND: Diabetes mellitus (DM) is regarded as a new risk factor for hepatocellular carcinoma (HCC), but few studies have focused on the potential role of DM in the progression of cirrhosis to HCC as well as in patients with simple HBV infection. METHODS: A cohort of 1028 patients, treated at our hospital and with a hospital discharge diagnosis of HCC and/or cirrhosis, was screened. Among them, 558 were diagnosed with chronic HBV infection and 370 were analyzed statistically according to the diagnostic, inclusion and exclusion criteria. The demographic, clinical, metabolic, virological, biochemical, radiological and pathological features were analyzed and the multivariate logistic regression model was used to determine the potential role of DM. RESULTS: In 248 cirrhotic patients, 76 were diabetic and their mean duration of DM was 4.6 years. In 122 HCC patients with cirrhosis, 25 were diabetic and their mean duration of DM was 4.4 years. Univariate analysis showed that compared with cirrhotic patients, the HCC patients had a higher percentage in males (P=0.001), a lower percentage in DM patients (P=0.039), a higher percentage in cigarette smokers (P=0.005), a higher percentage in patients with AFP】400 ng/mL (P【0.001), higher values of white blood cells (P【0.001), hemoglobin (P【0.001) and platelet (P【0.001), increased levels of ALT (P【0.001) and GGT (P【0.001), higher total bilirubin (P=0.018) and albumin levels (P【0.001), and a lower international normalized ratio (P【0.001). Multivariate logistic regression analysis showed that DM was anindependent associated factor for HCC [odds ratio (OR)=0.376; 95% CI, 0.175-0.807; P=0.012]. Even after the HCC patients were restricted to those with decompensated cirrhosis and compared with decompensated cirrhotic patients, the similar result was observed (OR=0.192; 95% CI, 0.054-0.679; P=0.010). CONCLUSIONS: DM is an independent factor in the progression of cirrhosis to HCC, but the role may be contrary to our current viewpoint. To clarify the causal relationship of DM and HCC, prospective and experimental studies are required.

Is diabetes mellitus a risk factor for pancreatic cancer?

The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long period of time.The importance of this topic is due to two main causes:the possible use of recent onset diabetes as a marker of the disease and,in particular,as a specific marker of pancreatic cancer,and the selection of a population at risk for pancreatic cancer.Thus,we decided to make an in-depth study of this topic;thus,we carried out an extensive literature search in order to re-assess the current knowledge on this topic.Even if diabetes is found a decade before the appearance of pancreatic cancer as reported in meta-analytic studies,we cannot select those patients already having non detectable pancreatic cancer,at least with the imaging and biological techniques available today.We believe that more studies are necessary in order to definitively identify diabetes mellitus as a risk factor for pancreatic cancer taking into consideration that approximately 10 years are needed to diagnose symptomatic pancreatic cancer.At present,the answer to the as to whether diabetes and pancreatic cancer comes first similar to the adage of the chicken and the egg is that diabetes is the egg.

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm,was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis,the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature,including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include,total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199and CEA levels for a suspicious cystic pancreatic mass.

Post-acute pancreatitis diabetes:A complication waiting for more recognition and understanding

Post-acute pancreatitis diabetes(PAPD)is the second most common type of diabetes below type 2 diabetes mellitus.Due to the boom in research on this entity carried out during the last decade,its recognition has increased.However,much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis(AP).Recent prospective cohort studies show that its incidence is about 23%globally and 34.5%in patients with severe AP.With the overall increase in the incidence of AP this complication will be certainly seen more frequently.Due to its high morbidity,mortality and difficult control,early detection and treatment are essential.However,its risk factors and pathophysiological mechanisms are not clearly defined.Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes.This review will show the evidence published so far on the incidence and prevalence,risk factors,possible pathophysiological mechanisms,clinical outcomes,clinical characteristics and preventive and corrective management of PAPD.Some important gaps needing to be clarified in forthcoming studies will also be discussed.

Magnetic resonance imaging for acute pancreatitis in type 2 diabetes patients

Type 2 diabetes mellitus(T2DM)and its complications have significantly increased the burden of mortality and disability globally,making diabetes one of the most dangerous and prevalent chronic diseases.Acute pancreatitis(AP)is one of the most frequent gastrointestinal causes for hospital admission,which is a common exocrine pancreatic inflammatory disease that can cause severe abdominal pain and multiple organ dysfunction.There is an inseparable relationship between AP and diabetes.Diabetes is a high risk factor of AP,and patients with AP can develop pancreatogenic diabetes.In T2DM patients,the incidence rate of AP is significantly higher than that of the general population,and the clinical symptoms are more severe,with the majority of cases being moderate to severe AP.This review briefly introduces the pathogenesis and clinical features of AP in T2DM patients,focusing on the magnetic resonance imaging(MRI)manifestations of AP in T2DM patients.Our aim is to evaluate the severity of AP in patients with T2DM by MRI,so as to help clinicians assess the patient's condition and prognosis.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose homeostasis.Voltage-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of insulin.The epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine cells.However,there is no reported study on the function of ENaC in theβ-cells.In the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-cells.In the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was increased.Whenα-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly reduced.On the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 cells.However,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by palmitate.Furthermore,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress pathways.These results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell dysfunction.In conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.

Mannogalactoglucan from mushrooms protects pancreatic islets via restoring UPR and promotes insulin secretion in TIDM mice

Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.

Pancreatic head excavation for tissue diagnosis may reduce unnecessary pancreaticoduode- nectomies in the setting of chronic pancreatitis

BACKGROUND： The necessity to obtain a tissue diagnosis of cancer prior to pancreatic surgery still remains an open debate. In fact, a non-negligible percentage of patients under- going pancreaticoduodenectomy （PD） for suspected cancer has a benign lesion at final histology. We describe an approach for patients with diagnostic uncertainty between cancer and chronic pancreatitis, with the aim of minimizing the incidence of PD for suspicious malignancy finally diagnosed as benign disease. METHODS： Eighty-eight patients （85.4%） with a clinicoradio- logical picture highly suggestive for malignancy received for- mal PD （group 1）. Fifteen patients （14.6%） in whom preopera- tive diagnosis was uncertain between pancreatic cancer and chronic pancreatitis underwent pancreatic head excavation （PHEX） for intraoperative tissue diagnosis （group 2）： those diagnosed as having cancer received PD, whereas those with chronic pancreatitis received pancreaticojejunostomy （P]）. RESULTS： No patient received PD for benign disease. All pa- tients in group I had adenocarcinoma on final histology. Eight patients of group 2 （53.3%） received PD after intraoperative diagnosis of cancer, whereas 7 （46.7%） received PJ because no malignancy was found at introperative frozen sections. No signs of cancer were encountered in patients receiving PHEX and PJ after a median follow-up of 42 months. Overall survival did not differ between patients receiving PD for cancer in the group 1 and those receiving PD for cancer after PHEX in the group 2 （P=0.509）. CONCLUSION： Although the described technique has been used in a very selected group of patients, our results suggest that PHEX for tissue diagnosis may reduce rates of unnecessary PD, when the preoperative diagnosis is uncertain between cancer and chronic pancreatitis.