Functional and structural adaptations in the pancreatic α-cell and changes in glucagon signaling during protein malnutrition

Chronic malnutrition leads to multiple changes in β-cell function and peripheral insulin actions to adapt glucose homeostasis to these restricted conditions. However, despite glucose homeostasis also depends on glucagon effects, the role of α-cells in malnutrition is largely unknown. Here, we studied α-cell function and hepatic glucagon signaling in mice fed with low-protein (LP) or normal-protein diet for 8 wk after weaning. Using confocal microscopy, we found that inhibition of Ca2? signaling by glucose was impaired in α-cells of LP mice. Consistent with these findings, the ability of glucose to inhibit glucagon release in isolated islets was also diminished in LP mice. This altered secretion was not related with changes in either glucagon gene expression or glucagon content. A morphometric analysis showed that α-cell mass was significantly increased in malnourished animals, aspect that was probably related with their enhanced plasma glucagon levels. When we analyzed the hepatic function, we observed that the phosphorylation of protein kinase A and cAMP response-binding element protein in response to fasting or exogenous glucagon was impaired in LP mice. Additionally, the up-regulated gene expression in response to fasting observed in the hepatic glucagon receptor as well as several key hepatic enzymes, such as peroxisome proliferator-activated receptor γ, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase, was altered in malnourished animals. Finally, liver glycogen mobilization in response to fasting and the ability of exogenous glucagon to raise plasma glucose levels were lower in LP mice. Therefore, chronic protein malnutrition leads to several alterations in both the α-cell function and hepatic glucagon signaling.     

Role of leptin in the pancreatic β-cell: effects and signaling pathways

Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic β-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the β-cell, and their activation directly inhibits insulin secretion from these endocrine cells. The effects of leptin on insulin occur also in the long term, since this hormone inhibits insulin gene expression as well. Additionally, β-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the β-cell are triggered by leptin as a result of the large diversity of signaling pathways that this hormone is able to activate in the endocrine pancreas. Therefore, leptin can participate in glucose homeostasis owing to different levels of modulation of the pancreatic β-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of β-cell function in obesity states. In the present review, we will discuss all these issues with special emphasis on the effects and pathways of leptin signaling in the pancreatic β-cell.     

Radiofrequency is a secure and effective method for pancreatic transection in laparoscopic distal pancreatectomy: results of a randomized, controlled trial in an experimental model

Background

Postoperative pancreatic fistula (PPF) is the most frequent and serious complication after laparoscopic distal pancreatectomy (LDP). Our goal was to compare the performance, in terms of PPF prevention, and safety of a radiofrequency (RF)-assisted transection device versus a stapler device in a porcine LDP model.

Methods

Thirty-two animals were randomly divided into two groups to perform LDP using a RF-assisted device (RF group; n = 16) and stapler device (ST group; n = 16) and necropsied 4 weeks after surgery. The primary endpoint was the incidence of PPF. Secondary endpoints were surgery/transection time, intra/postoperative complications/deaths, postoperative plasmatic amylase and glucose concentration, peritoneal liquid amylase and interleukin 6 (IL-6) concentrations, weight variations, and histopathological changes.

Results

Two clinical and one biochemical PPF were observed in the ST and RF groups respectively. Peritoneal amylase concentration was significantly higher in the RF group 4 days after surgery, but this difference was no longer present at necropsy. Both groups presented a significant decrease in peritoneal IL-6 concentration during the postoperative follow-up, with no differences between the groups. RF group animals showed a higher postoperative weight gain. In the histopathological exam, all RF group animals showed a common pattern of central coagulative necrosis of the parenchymal surface, surrounded by a thick fibrosis, which sealed main and secondary pancreatic ducts and was not found in ST group.

Conclusions

The fibrosis caused by an RF-assisted device can be at least as safe and effective as stapler compression to achieve pancreatic parenchyma sealing in a porcine LDP model.     

Immunohistochemical detection of interleukin-12 and interferon-gamma in pigs experimentally infected with Mycoplasma hyopneumoniae

The expression of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) was examined immunohistochemically in the lungs of pigs aged 21 days infected experimentally with Mycoplasma hyopneumoniae (Mh). Ten pigs were inoculated intranasally with Mh and killed in pairs weekly from 7 to 35 days post-infection (dpi). Immunolabelling for IL-12 and IFN-gamma was usually associated with inflammation, particularly in macrophages and lymphocytes in the thickened alveolar septa and in the hyperplastic bronchus-associated lymphoid tissue (BALT). Cells positive for both cytokines were detected at 7 dpi, their numbers increasing at 14 and 21 dpi, and slightly decreasing thereafter. The results suggest that IL-12 and IFN-gamma play a role in pulmonary defence mechanisms against Mh infection.     

Facial nerve injury during temporal artery biopsy

Temporal artery biopsy is considered the gold standard investigation of giant cell arteritis and is recommended in suspected cases despite a sensitivity of 81–91%. This review highlights the potential risk of facial nerve injury during temporal artery biopsy and introduces recent advances in the emerging role of imaging modalities. When these non-invasive techniques are used in conjunction with American College of Rheumatology scoring, which includes clinical features and biochemical test results, temporal artery biopsy may be avoided in selected cases.     

Role of preoperative carbohydrate loading: a systematic review

INTRODUCTION

Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery.

METHODS

All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles.

RESULTS

Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported.

CONCLUSIONS

Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.     

Serology and ultrasound for diagnosis of choledocholithiasis

Introduction

Magnetic resonance cholangiopancreatography (MRCP) is not a routine investigation to exclude choledocholithiasis unless there is clinical or biochemical suspicion of common bile duct (CBD) stones. This study attempted to determine which radiological or serological parameters best predicted CBD stones.

Methods

All patients undergoing MRCP from 2005 to 2011 were selected. Patients with pancreatitis were excluded. Liver function tests (LFTs) at admission and prior to MRCP were recorded, as was abdominal ultrasonography and MRCP results. Parameters measured routinely on LFTs included alkaline phosphatase (ALP), alanine transaminase (ALT) and bilirubin. Receiver operating characteristic curve area analysis (area under the curve [AUC]) and chi-squared analysis were undertaken.

Results

Overall, 195 patients were identified, 71 of whom had CBD stones on MRCP. Raised ALP levels on admission demonstrated a correlation with CBD stones (AUC: 0.619, odds ratio [OR]: 3.16, p=0.06). At ultrasonography, a dilated CBD (OR: 3.76, p<0.001) and intrahepatic duct dilation (OR: 5.56, p<0.001) were highly significant predictors. However, only 37% of patients had a dilated CBD on ultrasonography. Ongoing elevation of LFT parameters, particularly ALP (AUC: 0.707, OR: 4.64, p<0.001) and ALT (AUC: 0.646, OR: 5.40, p<0.001), displayed a significant correlation with CBD stones.

Conclusions

Ongoing (even if minor) elevations of liver function test parameters should prompt the need to exclude CBD stones even in the presence of a normal CBD diameter on ultrasonography.