Pancreatic Secretion Research Articles

Long Noncoding RNA-5657 Inhibits the Proliferation of Pancreatic Cells and Insulin Secretion in Gestational Diabetes by Inhibiting the NADPH Oxidase 4 (NOX4)

Multiple comorbidities are observed during pregnancy and there are many challenges for pregnant women with a previous history of diabetes. Pancreatic β-cell dysfunction is associated with gestational diabetes mellitus (GDM). This study intends to explore LncRNA-5657’s effect on proapoptotic cell proliferation and insulin secretion in gestational diabetes. Real-time quantitative fluorescence PCR measured LncRNA-5657 expression in GDM patient placental tissues along with analysis of cell activity, proliferation and insulin secretion by MTT assay, BrdU staining and ELISA. The relation between LncRNA-5657 and NOX4 was assessed by dual luciferase reporter assay. LncRNA-5657 was overexpressed in placental tissue of GDM patients compared to normal pregnant women. LncRNA-5657 overexpression promoted cell proliferation and insulin secretion, which was reversed by LncRNA-5657 downregulation. In addition, LncRNA-5657 negatively regulated NOX4 expression. Overexpression of NOX4 abolished the effect of LncRNA-5657 mimics on pancreatic β-cells, and knockdown of LncRNA-5657 promoted insulin secretion by upregulating NOX4 expression. In conclusion, LncRNA-5657 inhibits insulin secretion and β-cell proliferation by targeting NOX4, indicating that LncRNA-5657 might be a novel target for the treatment of GDM.

Mind the Gap—Disconnected Duct Syndrome

Disconnected duct syndrome (DDS) is an adverse sequela of acute necrotizing pancreatitis in which there is disruption of the pancreatic duct leading to a failure to deliver pancreatic secretions into the duodenum. Its presentation may range from a persistent external pancreatic fistula to a treatment-resistant pancreatic pseudocyst. The diagnosis is often delayed in the acute setting if there is concurrent necrosis as management is often directed to the associated peripancreatic fluid collection. A combination of imaging modalities may be required to evaluate ductal anatomy. No definitive consensus has been achieved regarding the optimal treatment strategy for DDS, and there is a lack of published level I evidence on the topic. Treatment should be tailored to each individual patient, depending on the anatomy of ductal disruption, the presence of sepsis, the degree of physiological derangement, and the patients' performance status. Patients with DDS represent a specific cohort of patients with complex pancreatic disease that requires the input from a diverse multidisciplinary team to ensure that a good clinical outcome can be achieved.

Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity.

Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secretion in human islets, while GLUT2 is the key isoform in rodent islets. However, it is unclear whether other glucose transporters also contribute to insulin secretion by pancreatic islets. Herein, we show that SLC2A6 (GLUT6) is markedly upregulated in pancreatic islets from genetically obese leptin-mutant (ob/ob) and leptin receptor-mutant (db/db) mice, compared to lean controls. Furthermore, we observe that islet SLC2A6 expression positively correlates with body mass index in human patients with type 2 diabetes. To investigate whether GLUT6 plays a functional role in islets, we crossed GLUT6 knockout mice with C57BL/6 ob/ob mice. Pancreatic islets isolated from ob/ob mice lacking GLUT6 secreted more insulin in response to high-dose glucose, compared to ob/ob mice that were wild type for GLUT6. The loss of GLUT6 in ob/ob mice had no adverse impact on body mass, body composition, or glucose tolerance at a whole-body level. This study demonstrates that GLUT6 plays a role in pancreatic islet insulin secretion in vitro but is not a dominant glucose transporter that alters whole-body metabolic physiology in ob/ob mice.

Shortening the Biliopancreatic Limb Length of One Anastomosis Gastric Bypass Maintains Glucose Homeostasis Improvement with Limited Weight Loss.

One anastomosis gastric bypass (OAGB) is associated with similar metabolic improvements and weight loss as Roux-en-Y gastric bypass (RYGB). However, this bariatric procedure is still controversial as it is suspected to result in undernutrition. Reducing the size of the biliopancreatic limb of OAGB could be essential to maintain positive outcomes while preventing side effects. The objective of this study was to compare and contrast outcomes of OAGB with two different biliopancreatic limb lengths to RYGB and Sham surgery in obese and non-obese rats. Lean and diet-induced obese Wistar rats were operated on RYGB, OAGB with a short (15 cm OAGB-15) or a long (35 cm OAGB-35) biliopancreatic limb or Sham surgery. Body weight and food intake were monitored over 30 weeks, and rats underwent oral glucose and insulin tolerance tests with a pancreatic and gut hormone secretion assay. Macronutrient absorption was determined by fecal analyses. Statistical analyses used non-parametric one-way or two-way ANOVA tests. Compared to Sham rats, RYGB, OAGB-15 and OAGB-35 rats displayed a significant reduced weight. Weight loss was greater after OAGB-35 than after OAGB-15 or Sham surgery because of transient malabsorption. All OAGB- and RYGB-operated rats displayed an improved pancreatic and gut hormone secretion in response to a meal compared to Sham rats, these effects were independent of limb length, rat weight, and maintained overtime. In conclusion, glucose homeostasis was similarly improved in obese and non-obese OAGB-15 and OAGB-35 rats suggesting that shortening the biliopancreatic limb can improve the metabolic parameters without a major influence on weight.

Insulin Resistance in Chronic Hepatitis C Non Diabetic Patients

Background: Patients with chronic hepatitis have impaired glucose metabolism with hyperinsulinemia and insulin resistance, this hyperinsulinemia has been shown to be due to decreased insulin catabolism rather than increased pancreatic insulin secretion. We aimed to evaluate insulin resistance in non-diabetic patients with chronic hepatitis C virus infection. Subjects and methods: The study was a case-control study conducted in Tropical Medicine and Gastroenterology Department King Abdullah University Hospital. 60 patients and 30 healthy controls were included in the study. The patients were classified into two groups: Group A: 30 patients with chronic hepatitis C infection were selected with positive HCV RNA in serum for at least 6 months; Patients were not receiving anti-viral therapy at the time of sampling. They showed no evidence of cirrhosis. Group B: 30 patients with HCV related liver cirrhosis. They were divided according to Child Pugh score; twenty patients with HCV related compensated liver cirrhosis (Child A). Ten patients with HCV related decompensated liver cirrhosis (Child B and C). Group C: The control group: included 30 healthy individuals. All patients and controls were subjected to the following: Liver function tests: Alanine transaminase (ALT), Aspartate transaminase (AST), total and direct bilirubin, total protein, serum albumin. Prothrombin time (PT) & international normalization ratio (INR). Renal function tests: Blood urea nitrogen (BUN), Na, K. Complete blood count. Alpha fetoprotein (αFP). Diagnosis of chronic hepatitis C infection was based on positive HCV by PCR, persistent elevation of liver enzymes more than 6 months and liver biopsy for some of the patients. Anti-hepatitis C virus antibody (HCV Ab) using third generation enzyme linked immune sorbant assay (ELISA) test., Hepatitis B virus (HBV): HBVsAg., Overnight fasting and two hours postprandial blood glucose level. Fasting serum insulin of everyone. Insulin resistance was determined via the Homeostasis Model assessment (HOMA-IR) by the following equation: - Insulin resistance: Fasting insulin (μu/ml) x Fasting glucose (mmol/L) 22.5 An index value of > 2.5 was defined as IR. This cutoff value was chosen because studies suggested that a HOMA-IR of 2.4-3.0 is probably suitable to define IR in CHC patients. Blood samples were collected after 12 hours of overnight fasting. Results: We found that out of 30 CHC and 30 LC (20 compensated LC, 10 de compensated LC) 8 (26.7%); 8 (40%) patients and 5(50%) respectively had HOMA-IR levels greater than 2.5, which is consistent with IR diagnosis. Decompensated cirrhotic patients showed higher frequency of IR compared to CHC and compensated cirrhotic patients. Conclusion: In chronic hepatitis C patients, HOMA-IR, fasting serum insulin and fasting blood glucose were significantly higher than healthy controls (p <0.0001).

Bioinformatics Analysis Based on TCGA: MUC16 Mutation Correlates with Clinical Outcome in Gastric Cancer.

The prognosis of gastric cancer (GC) is difficult to predict due to the disease's complex genetic and phenotypic characteristics. MUC16 has been reported to be involved in the progression of several tumors. In this study, we aimed to explore whether MUC16 mutation had any impact on the prognosis or treatments of GC patients. Additionally, this analysis uncovered possible critical pathways related with these systems. On the cBioPortal, we were able to locate the pertinent data of patients with MUC16 mutations. And then, GSEA analysis identified differences in mRNA levels between mutant and wild-type MUC16 patients in terms of biological function annotation and pathways. The KEGG and GO analyses were also performed using the differentially expressed genes (DEGs). There were 139 individuals with GC who had the MUC16 mutation, which accounts for 32 percent, and the remaining patients had the MUC16 wild type. Survival assays revealed that patients with the MUC16 mutation had longer overall survival and disease-free survival. GSEA analysis revealed that cell cycle, cysteine and methionine metabolism, Huntington's disease, one carbon pool by folate, pyrimidine metabolism, pyruvate metabolism, RNA degradation, spliceosome, and valine leucine and isoleucine degradation were distinctly enriched in patients with MUC16 mutation type. Moreover, we identified 323 DEGs. Among them, 162 genes were upregulated, and 161 genes were downregulated. GO and KEGG assays indicated DEGs as enriched in pancreatic secretion, neuroactive ligand-receptor interaction, protein digestion and absorption, fat digestion and absorption, and glycerolipid metabolism. Overall, our data revealed that the MUC16 mutation in GC may affect the development of patients by altering several genes and pathways, indicating the importance of MUC16 mutation in the treatments of GC on an individual basis.

Identification of a glycolysis- and lactate-related gene signature for predicting prognosis, immune microenvironment, and drug candidates in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD), a malignant gastrointestinal tumor, has the characteristics of high mortality and poor prognosis. Even in the presence of oxygen, the Warburg effect, a major metabolic hallmark of almost all cancer cells, is characterized by increased glycolysis and lactate fermentation, which supports biosynthesis and provides energy to sustain tumor cell growth and proliferation. However, a thorough investigation into glycolysis- and lactate-related genes and their association with COAD prognosis, immune cell infiltration, and drug candidates is currently lacking. Methods: COAD patient data and glycolysis- and lactate-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases, respectively. After univariate Cox regression analysis, a nonnegative matrix factorization (NMF) algorithm was used to identify glycolysis- and lactate-related molecular subtypes. Least absolute shrinkage and selection operator (LASSO) Cox regression identified twelve glycolysis- and lactate-related genes (ADTRP, ALDOB, APOBEC1, ASCL2, CEACAM7, CLCA1, CTXN1, FLNA, NAT2, OLFM4, PTPRU, and SNCG) related to prognosis. The median risk score was employed to separate patients into high- and low-risk groups. The prognostic efficacy of the glycolysis- and lactate-related gene signature was assessed using Kaplan–Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The nomogram, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were employed to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on differentially expressed genes (DEGs) from the high- and low-risk groups. Using CIBERSORT, ESTIMATE, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. The tumor mutational burden (TMB) and cytolytic (CYT) activity scores were calculated between the high- and low-risk groups. Potential small-molecule agents were identified using the Connectivity Map (cMap) database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT–PCR) assays were conducted. Results: We identified four distinct molecular subtypes of COAD. Cluster 2 had the best prognosis, and clusters 1 and 3 had poor prognoses. High-risk COAD patients exhibited considerably poorer overall survival (OS) than low-risk COAD patients. The nomogram precisely predicted patient OS, with acceptable discrimination and excellent calibration. GO and KEGG pathway enrichment analyses of DEGs revealed enrichment mainly in the “glycosaminoglycan binding,” “extracellular matrix,” “pancreatic secretion,” and “focal adhesion” pathways. Patients in the low-risk group exhibited a larger infiltration of memory CD4+ T cells and dendritic cells and a better prognosis than those in the high-risk group. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. We predicted six potential small-molecule agents binding to the core target of the glycolysis- and lactate-related gene signature. ALDOB and APOBEC1 mRNA expression was increased in COAD tissues, whereas CLCA1 and OLFM4 mRNA expression was increased in normal tissues. Conclusion: In summary, we identified molecular subtypes of COAD and developed a glycolysis- and lactate-related gene signature with significant prognostic value, which benefits COAD patients by informing more precise and effective treatment decisions.

Ethanol inhibits pancreatic projecting neurons in the dorsal motor nucleus of the vagus

Alcohol use disorder (AUD) is a rapidly growing concern in the United States. Current trending escalations of alcohol use are associated with a concurrent rise in alcohol-related end-organ damage, increasing risk for further diseases. Alcohol-related end-organ damage can be driven by autonomic nervous system dysfunction, however studies on alcohol effects on autonomic control of end-organ function are lacking. Alcohol intake has been shown to reduce insulin secretions from the pancreas. Pancreatic insulin release is controlled in part by preganglionic parasympathetic motor neurons residing in the dorsal motor nucleus of the vagus (DMV) that project to the pancreas. How these neurons are affected by alcohol exposure has not been directly examined. Here we investigated the effects of acute ethanol (EtOH) application on DMV pancreatic-projecting neurons with whole-cell patch-clamp electrophysiology. We found that bath application of EtOH (50 mM) for greater than 30 min significantly enhanced the frequency of spontaneous inhibitory post synaptic current (sIPSC) events of DMV pancreatic-projecting neurons suggesting a presynaptic mechanism of EtOH to increase GABAergic transmission. Thirty-minute EtOH application also decreased action potential firing of these neurons. Pretreatment of DMV slices with 20 μM fluoxetine, a selective serotonin reuptake inhibitor, also increased GABAergic transmission and decreased action potential firing of these DMV neurons while occluding any further effects of EtOH application, suggesting a critical role for serotonin in mediating EtOH effects in the DMV. Ultimately, decreased DMV motor output may lead to alterations in pancreatic secretions. Further studies are needed to fully understand EtOH’s influence on DMV neurons as well as the consequences of changes in parasympathetic output to the pancreas.

MRI Evaluation of Indomethacin Suppositories in the Prevention of Complications of Pancreatitis and Hyperamylasemia after Choledocholithiasis ERCP Based on Image Denoising Algorithm.

Objective To explore the value of MRI evaluation of indomethacin suppositories in the prevention of pancreatitis and hyperamylasemia in patients with common bile duct calculi after endoscopic retrograde cholangiopancreatography (ERCP) based on image denoising algorithm. Methods A retrospective analysis in August 2020 to December 2021. Because of the common bile duct calculi hospitalized parallel ERCP operation, 89 cases of patients, according to the different postoperative treatments, were divided into group A (n = 44) and group B (n = 45), in which A set of separate application inhibits the pancreatic enzyme secretion after surgery drug treatment, and B group on the basis of group A linked with indole beauty Xinshuan treatment. The incidence of postoperative pancreatitis and hyperamylasemia was compared between the two groups. The levels of serum amylase were compared between the two groups. Patients in group B were diagnosed with pancreatitis by conventional MRI and MRI with denoising algorithm, respectively, and the imaging characteristics and diagnosis rate differences of the two methods were observed. ROC curve was drawn to evaluate the diagnostic efficacy of MRI denoising algorithm for postoperative pancreatitis and serum amylase level detection for hyperamylasemia. Results The incidence of postoperative pancreatitis and hyperamylasemia in group B was significantly lower than that in group A (P < 0.05). There were 6 cases of postoperative pancreatitis in group B, 2 cases (33.33%) were diagnosed by conventional MRI, and 5 cases (83.33%) were diagnosed by MRI based on denoising algorithm. Although there was no significant difference in diagnosis rate between the two methods, the number of cases of pancreatitis diagnosed by MRI based on denoising algorithm was slightly higher than that by conventional MRI. Compared with conventional MRI images, MRI images with denoising algorithm showed that the number of cases with pancreatic swelling, the number of cases with pancreatic duct/bile duct dilation, and the number of cases with abdominal effusion were all high (all P < 0.05). ROC results showed that the area under the curve of MRI with denoising algorithm for the diagnosis of postoperative pancreatitis was 0.855, and the sensitivity was 89.40%. The specificity was 83.20%, and the area under the curve of serum amylase for postoperative hyperamylasemia was 0.893, the sensitivity was 89.80%, and the specificity was 85.20%, all of which had high diagnostic efficacy. Conclusion MRI results of denoising algorithm suggest that indomethacin suppositories can effectively reduce the incidence of postoperative pancreatitis and hyperamylasemia after ERCP, which is worthy of clinical application.

The Role of Statins (HMG-CoA Reductase Inhibitors) on Insulin Secretion from the Islets of Langerhans: A Systematic Review

Context: Statins are administered to decrease atherosclerosis in patients with coronary heart disease. These drugs enhance the risk of diabetes by affecting islets insulin secretion. Objectives: Therefore, this systematic review investigates the effect of statins on insulin secretion of islets of Langerhans in the related original studies. Methods: A preliminary search was performed in the PubMed, Scopus, Web of Science, and ProQuest databases. The search strategy terms were statin (hydroxymethylglutaryl-CoA reductase inhibitors), insulin secretion, and islets of Langerhans. The search elements were evaluated using the Mesh term system. Limits were used to include only review articles and no limits were set on language. The quality of the method and risk of bias was assessed by its tool. Results: After removing irrelevant articles to the subject, 20 articles fulfilled the inclusion criteria. In vivo studies revealed that pravastatin and rosuvastatin increase and decrease islets insulin secretion, while atorvastatin and fluvastatin reduced this variable, and pitavastatin had no effect. The results of in vitro studies showed that pravastatin and induced both increasing and decreasing effects on insulin secretion from the pancreatic islet cells. Also, administration of atorvastatin, rosuvastatin, fluvastatin, pitavastatin, simvastatin, and lovastatin decreased islet insulin secretion in the medium. Conclusions: Pravastatin could enhance pancreatic islet insulin secretion while other statins reduced this variable. Finally, the contradictory effect of statins on islets’ insulin secretion can indicate the existence of laboratory and clinical research in this regard.

In vitro assessment of pancreatic hormone secretion from isolated porcine islets.

The potential use of porcine islets for transplantation in humans has triggered interest in understanding porcine islet physiology. However, the number of studies dedicated to this topic has remained limited, as most islet physiologists prefer to use the less time-consuming rodent model or the more clinically relevant human islet. An often-overlooked aspect of pig islet physiology is its alpha cell activity and regulation of its glucagon secretion. In vitro islet perifusion is a reliable method to study the dynamics of hormone secretion in response to different stimuli. We thus used this method to quantify and study glucagon secretion from pig islets. Pancreatic islets were isolated from 20 neonatal (14 to 21-day old) and 5 adult (>2 years) pigs and cultured in appropriate media. Islet perifusion experiments were performed 8 to 10 days post-isolation for neonatal islets and 1 to 2 days post-isolation for adult islets. Insulin and glucagon were quantified in perifusion effluent fractions as well as in islet extracts by RIA. Increasing glucose concentration from 1 mM to 15 mM markedly inhibited glucagon secretion independently of animal age. Interestingly, the effect of high glucose was more drastic on glucagon secretion compared to its effect on insulin secretion. In vivo, glucose injection during IVGTT initiated a quick (2-10 minutes) 3-fold decrease of plasmatic glucagon whereas the increase of plasmatic insulin took 20 minutes to become significant. These results suggest that regulation of glucagon secretion significantly contributes to glucose homeostasis in pigs and might compensate for the mild changes in insulin secretion in response to changes in glucose concentration.

EUS-Guided Rendezvous and Tractogastrostomy: A Novel Technique for Disconnected Pancreatic Duct Syndrome with External Pancreatic Fistula

Abstract Background and Aims External pancreatic fistula occurring in the setting of disconnected pancreatic duct syndrome leads to significant morbidity, often requiring surgery. The aim of this study is to report a new technique of endoscopic ultrasound (EUS)-guided rendezvous and tractogastrostomy in patients with disconnected pancreatic duct syndrome and external pancreatic fistula. Methods This study is retrospective analysis of the data of the patients with external pancreatic fistula who had undergone EUS-guided rendezvous and tractogastrostomy. Internalization of pancreatic secretions was performed by placing a stent between tract and the stomach. Technical success was defined as placement of stent between the tract and the stomach. Clinical success was defined as removal of external catheter and absence of peripancreatic fluid collection, ascites or external fistula at 3 months after the tractogastrostomy. Results Four patients, all male, with median age of 33.5 years (range: 29–45), underwent EUS-guided tractogastrostomy. Technical and clinical success was 100%, without any procedure related complication. External catheter could be removed in all the patients. During the median follow-up of 10.5 months (range: 8–12), two patients had stent migration and peripancreatic fluid collection, which were managed by EUS-guided internal drainage. Conclusions EUS-guided rendezvous and tractogastrostomy are a safe and effective technique for the treatment of external pancreatic fistula.

Effects of an isoenergetic multifactorial diet on pancreatic fat and insulin secretion in patients with type 2 diabetes: A randomized controlled trial

Background and Aims : Pancreatic fat (PF) accumulation may impair beta-cell function. We investigated whether an isocaloric diet able to reduce liver fat in type 2 diabetes (T2D) also affected PF and postprandial insulin secretion.

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

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

Combined Illumina and Pacbio sequencing technology on transcriptome analysis reveals several key regulations during the early development of American shad (Alosa sapidissima)

This study was conducted to examine the early developmental processes and mechanisms in American shad (Alosa sapidissima). Both Illumina and Pacific Biosciences (PacBio) sequencing were employed to analyze the transcriptome at embryonic, larval, and fingerling stages. Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis was performed to validate the reproducibility and repeatability of identified differentially expressed genes (DEGs). 88.91 G of clean data from Illumina sequencing were retained, and 57.0 G of subreads were obtained from PacBio RS II sequencing. It was observed that compared to embryonic samples, 6070 DEGs were screened in larval. These DEGs were mainly enriched in Gene Ontology (GO) terms of cell or organ differentiation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of protein digestion and absorption, pancreatic secretion, and phototransduction. There were 2897 DEGs found in the fingerling_vs_larva. These DEGs primarily participated in KEGG pathways related to the carbon metabolism, microbial metabolism, and amino acid metabolism. In conclusion, the molecular developmental profile showed that the larva existed as a very different organism from the embryo and fingerling during a short period of its early life history. The development related to organ formation and the visual system was more pronounced from embryo to larva development. At the same time, the function of digestion and stress response were activated, thereby generating from the larval to fingerling.

Dual pancreatic adrenergic and dopaminergic signaling as a therapeutic target of bromocriptine

SummaryBromocriptine is approved as a diabetes therapy, yet its therapeutic mechanisms remain unclear. Though bromocriptine’s actions have been mainly attributed to the stimulation of brain dopamine D2 receptors (D2R), bromocriptine also targets the pancreas. Here, we employ bromocriptine as a tool to elucidate the roles of catecholamine signaling in regulating pancreatic hormone secretion. In β-cells, bromocriptine acts on D2R and α2A-adrenergic receptor (α2A-AR) to reduce glucose-stimulated insulin secretion (GSIS). Moreover, in α-cells, bromocriptine acts via D2R to reduce glucagon secretion. α2A-AR activation by bromocriptine recruits an ensemble of G proteins with no β-arrestin2 recruitment. In contrast, D2R recruits G proteins and β-arrestin2 upon bromocriptine stimulation, demonstrating receptor-specific signaling. Docking studies reveal distinct bromocriptine binding to α2A-AR versus D2R, providing a structural basis for bromocriptine’s dual actions on β-cell α2A-AR and D2R. Together, joint dopaminergic and adrenergic receptor actions on α-cell and β-cell hormone release provide a new therapeutic mechanism to improve dysglycemia.

Ghrelin as a promising biological marker in cardiovascular disease

This review highlights the current literature data on the peptide hormone ghrelin. Ghrelin is a 28-amino-acid peptide, which is the only known peptide hormone modified with fatty acids. Ghrelin is a natural receptor ligand that stimulates the secretion of growth hormones. In addition to the stomach, ghrelin is expressed in many organs such as the duodenum, jejunum, ileum, colon, lungs, heart, pancreas, kidneys, testicles, pituitary gland, and hypothalamus. The main biological functions of this peptide include growth hormone secretion, appetite stimulation, modulation of gastric acid secretion and motility, and an increase in endocrine and exocrine pancreatic secretions. Reference intervals for ghrelin are 8.50216.6 pg/mL. The studies analyzed have shown a strong relationship between ghrelin and cardiovascular system function. Studies have also described the cardioprotective effects of ghrelin. However, the molecular mechanisms underlying the effects of ghrelin on the heart are not fully understood. A further deeper understanding of the role of ghrelin and future clinical studies are necessary to determine the diagnostic, prognostic, and possibly therapeutic significance of this biomarker.

Comparative Phosphoproteomic Profiling in the Prefrontal Cortex of Prenatally Stressed Male Offspring Rats

Many investigations have indicated that prenatal stress (PS) causes depressive-like disturbances in offspring rats. However, the underlying pathogenic mechanisms have not yet been fully elucidated. The prefrontal cortex (PFC) has been shown to play a role in susceptibility to stress during fetal development; thus, we focused our attention on differential protein phosphorylation in this region of PS-S (susceptibility to PS) offspring rats. The sucrose preference test was used to screen for susceptibility to PS. The validity of the prenatally stressed model was verified by other common depression-like behaviors. We used MS-based TMT quantitative proteomics in combination with the phosphopeptide enrichment method to compare phosphoproteomic profiling in the PFC of PS-S and control male offspring rats. In total, 3,418 phosphoproteins, 8,404 phosphopeptides, and 12,175 phosphosites were identified in this analysis. According to the screening criteria, 902 phosphopeptides increased and 609 decreased in the PFC of the PS-S group compared to the control rats. Gene ontology enrichment analysis indicated that the main enriched terms in the cellular component category were “synapse part,” “myelin sheath,” “synapse,” “neuron part,” and “axon.” The phosphoproteins enriched in the molecular function and biological process categories were mainly related to cytoskeleton- and projection morphogenesis-associated proteins. KEGG pathway enrichment analyses identified 30 significant KEGG pathways; the top five pathways included salivary secretion, endocrine and other factor-regulated calcium reabsorption, pancreatic secretion, and insulin secretion. Motifs such as ……_S_P…RR, ……S_PE……, ……_S_PV……, ……_S_P.H……, and …S…_S_PT…. were the top five motifs enriched in phosphorylated sites. PS may induce depressive-like behaviors in male offspring rats by regulating the phosphorylation of proteins mainly related to synapses, myelin sheaths, neurons, and the cytoskeleton. The phosphorylation of related proteins may act as key pathogenic hits. Data are available via ProteomeXchange with identifier PXD026563.

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery

Bariatric-metabolic surgery (BMS) in patients with obesity frequently leads to remission of concurrent type 2 diabetes mellitus (T2DM), even before body weight loss takes place. This is probably based on the correction of a dysmetabolic cycle in the gastrointestinal physiology of T2DM that includes increased vagus-dependent exocrine pancreatic secretion (EPS) and, hence, amplified digestion and nutrient absorption. The resultant chronic exposure of tissues to high plasma levels of glucose, fatty acids and amino acids causes tissue resistance to the actions of insulin and, at a later stage, β-cell dysfunction and reduction of insulin release. We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS, − hence reducing the digestion and absorption of nutrients -, and increasing incretin secretion as a result of increased delivery of unabsorbed nutrients to the distal intestine. This hypothesis is supported by surgical data from gastrointestinal malignancies and peptic ulcer operations that include TV, as well as by vagal blockade studies. We suggest that TV may result in a stable reduction of EPS, and that its combination with the appropriate type of BΜS, may enhance and sustain the salutary effects of the latter on T2DM.