Peptides (v.60, #C)
IFC (editorial board) (IFC).
Gayle & Richard Olson prize pages (III-IV).
Des-acyl-ghrelin (DAG) normalizes hyperlactacidemia and improves survival in a lethal rat model of burn trauma by Sulaiman Sheriff; Nijiati Kadeer; Lou Ann Friend; J. Howard James; J. Wesley Alexander; Ambikaipakan Balasubramaniam (1-7).
Critical illness, including burn injury, results in elevated plasma lactate levels. Dysregulation of PI3K/Akt signaling has been shown to play a predominant role in the inactivation of skeletal muscle PDC and, hence, in hyperlactacidemia in rat models of sepsis and endotoxemia. This observation, and our previous finding that DAG can reverse burn-induced skeletal muscle proteolysis through the activation of PI3K/Akt pathway, led us to hypothesize that DAG may also attenuate hyperlactacidemia in burn injury. Our investigations revealed that burn injury significantly elevated both skeletal muscle lactate production and plasma lactate levels. Moreover, this was accompanied in skeletal muscle by a 5–7 fold increase in mRNA expression of pyruvate dehydrogenase kinases (PDK) 2 and 4, and a ∼30% reduction in PDC activity. DAG treatment of burn rats completely normalized not only the mRNA expression of the PDKs and PDC activity, but also hyperlactacidemia within 24 h of burn injury. DAG also normalized epinephrine-induced lactate production by isolated skeletal muscles from normal rats. Moreover, DAG also improved survival in a lethal rat model of burn trauma. These findings with DAG may have clinical implications because chances of survival for critically ill patients are greatly improved if plasma lactate levels are normalized within 24 h of injury.
Keywords: Burn injury; Des-acyl-ghrelin (DAG); Hyperlactacidemia; PDC activity; PDK; Survival;
Elevated plasma visfatin levels correlate with conversion of laparoscopic cholecystectomy to open surgery in acute cholecystitis by Kai-Gang Xie; Xiao-Ping Teng; Shui-Yin Zhu; Xiong-Bo Qiu; Xiao-Ming Ye; Xiao-Ming Hong (8-12).
Visfatin correlates with inflammation and its levels in peripheral blood are associated with some inflammatory diseases. This study aimed to assess the relationship between plasma visfatin levels and conversion of laparoscopic cholecystectomy to open surgery in acute cholecystitis. One hundred and forty-six acute cholecystitis patients and 146 sex- and age-matched healthy controls were recruited and their plasma visfatin levels were determined using an enzyme immunoassay. 17 patients (11.6%) underwent conversion. Plasma visfatin levels were statistically significantly elevated in all patients (97.2 ± 41.8 ng/mL), those with (161.4 ± 71.3 ng/mL) or without conversion (88.7 ± 26.9 ng/mL), compared to controls (40.3 ± 13.3 ng/mL, all P < 0.001). A linear regression analysis showed that plasma visfatin levels were positively associated with plasma C-reactive protein levels (t = 0.510, P < 0.001). A logistic-regression analysis showed that age [odds ratio (OR) 1.160, 95% confidence interval (CI) 1.011–1.332, P = 0.035] and plasma visfatin levels (OR 1.035, 95% CI 1.005–1.066, P = 0.022) appeared to be the independent predictors of conversion. A receiver operating characteristic curve analysis found that plasma visfatin levels predicted conversion with high area under curve (AUC) (AUC, 850; 95% CI, 0.781–0.903). The AUC of the visfatin concentration was similar to that of age (AUC, 0.738; 95% CI, 0.659–0.807) (P = 0.188). Visfatin improved the AUC of age to 0.914 (95% CI, 0.856–0.954) (P = 0.011) using a combined logistic-regression model. Thus, high plasma levels of visfatin are associated with systemic inflammation, and may independently predict conversion of laparoscopic cholecystectomy to open surgery in acute cholecystitis.
Keywords: Visfatin; Acute cholecystitis; Conversion; Laparoscopic cholecystectomy; Open surgery;
Comparison of the performances of copeptin and multiple biomarkers in long-term prognosis of severe traumatic brain injury by Zu-Yong Zhang; Li-Xin Zhang; Xiao-Qiao Dong; Wen-Hua Yu; Quan Du; Ding-Bo Yang; Yong-Feng Shen; Hao Wang; Qiang Zhu; Zhi-Hao Che; Qun-Jie Liu; Li Jiang; Yuan-Feng Du (13-17).
Enhanced blood levels of copeptin correlate with poor clinical outcomes after acute critical illness. This study aimed to compare the prognostic performances of plasma concentrations of copeptin and other biomarkers like myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1 in severe traumatic brain injury. We recruited 102 healthy controls and 102 acute patients with severe traumatic brain injury. Plasma concentrations of these biomarkers were determined using enzyme-linked immunosorbent assay. Their prognostic predictive performances of 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1–3) were compared. Plasma concentrations of these biomarkers were statistically significantly higher in all patients than in healthy controls, in non-survivors than in survivors and in patients with unfavorable outcome than with favorable outcome. Areas under receiver operating characteristic curves of plasma concentrations of these biomarkers were similar to those of Glasgow Coma Scale score for prognostic prediction. Except plasma copeptin concentration, other biomarkers concentrations in plasma did not statistically significantly improve prognostic predictive value of Glasgow Coma Scale score. Copeptin levels may be a useful tool to predict long-term clinical outcomes after severe traumatic brain injury and have a potential to assist clinicians.
Keywords: Traumatic brain injury; Prognosis; Copeptin; Biomarkers;
Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury by Peter Bukovics; Endre Czeiter; Krisztina Amrein; Noemi Kovacs; Jozsef Pal; Andrea Tamas; Terez Bagoly; Zsuzsanna Helyes; Andras Buki; Dora Reglodi (18-22).
PACAP has well-known neuroprotective potential including traumatic brain injury (TBI). Its level is up-regulated following various insults of the CNS in animal models. A few studies have documented alterations of PACAP levels in human serum. The time course of post-ictal PACAP levels, for example, show correlation with migraine severity. Very little is known about the course of PACAP levels following CNS injury in humans and the presence of PACAP has not yet been detected in cerebrospinal fluid (CSF) of subjects with severe TBI (sTBI). The aim of the present study was to determine whether PACAP occurs in the CSF and plasma (Pl) of patients that suffered sTBI and to establish a time course of PACAP levels in the CSF and Pl. Thirty eight subjects with sTBI were enrolled with a Glasgow Coma Scale ≤8 on admission. Samples were taken daily, until the time of death or for maximum 10 days. Our results demonstrated that PACAP was detectable in the CSF, with higher concentrations in patients with TBI. PACAP concentrations markedly increased in both Pl and CSF in the majority of patients 24–48 h after the injury stayed high thereafter. In cases of surviving patients, Pl and CSF levels displayed parallel patterns, which may imply the damage of the blood–brain barrier. However, in patients, who died within the first week, Pl levels were markedly higher than CSF levels, possibly indicating the prognostic value of high Pl PACAP levels.
Keywords: Endogenous PACAP; Plasma; Cerebrospinal fluid; Traumatic brain injury; Neuroprotective; Blood–brain barrier;
Obestatin improves ischemia/reperfusion-induced renal injury in rats via its antioxidant and anti-apoptotic effects: Role of the nitric oxide by Mehmet Koç; Zarife Nigâr Özdemir Kumral; Naziye Özkan; Gülsün Memi; Ömer Kaçar; Serpil Bilsel; Şule Çetinel; Berrak Ç. Yeğen (23-31).
Obestatin was shown to have anti-inflammatory effects in several inflammatory models. To elucidate the potential renoprotective effects of obestatin, renal I/R injury was induced in male Sprague Dawley rats by placing a clamp across left renal artery for 60 min following a right nephrectomy. Clamp was released and the rats were injected with either saline or obestatin (10, 30, 100 μg/kg). In some experiments, obestatin (10 μg/kg) was administered with L-NAME (10 mg/kg) or L-Nil (0.36 mg/kg). Following a 24-h reperfusion, the rats were decapitated to measure serum creatinine and nitrite/nitrate levels, renal malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity and to assess cortical necrosis and apoptosis scores. Obestatin treatment reduced I/R-induced increase in creatinine levels, renal MPO activity and renal MDA levels, while renal GSH levels were significantly increased by obestatin. Histological analysis revealed that severe I/R injury and high apoptosis score in the kidney samples of saline-treated rats were significantly reduced and the cortical/medullary injury was ameliorated by obestatin. Expression of eNOS, which was increased by I/R injury, was further increased by obestatin, while serum NO levels were significantly decreased. iNOS inhibitor L-Nil reduced oxidative renal damage and improved the functional and histopathological parameters. I/R-induced elevation in eNOS expression, which was further increased by obestatin, was depressed by L-NAME and L-Nil treatments. The present data demonstrate that obestatin ameliorates renal I/R-injury by its possible anti-oxidative, anti-inflammatory and anti-apoptotic properties, which appear to involve the suppression of neutrophil accumulation and modulation of NO metabolism.
Keywords: Obestatin; Renal ischemia-reperfusion injury; Nitric oxide; Oxidative stress;
Antibacterial peptide nisin: A potential role in the inhibition of oral pathogenic bacteria by Zhongchun Tong; Longxing Ni; Junqi Ling (32-40).
Although the antimicrobial peptide nisin has been extensively studied in the food industry for decades, its application in the oral cavity remains to develop and evaluate its feasibility in treating oral common diseases. Nisin is an odorless, colorless, tasteless substance with low toxicity and with antibacterial activities against Gram-positive bacteria. These biologic properties may establish its use in promising products for oral diseases. This article summarizes the antibacterial efficiency of nisin against pathogenic bacteria related to dental caries and root canal infection and discusses the combination of nisin and common oral drugs.
Keywords: Nisin; Streptococcus mutans; Enterococcus faecalis; MTAD; MTADN;
Novel peptide VIP-TAT with higher affinity for PAC1 inhibited scopolamine induced amnesia by Rongjie Yu; Yanxu Yang; Zekai Cui; Lijun Zheng; Zhixing Zeng; Huahua Zhang (41-50).
A novel peptide VIP-TAT with a cell penetrating peptide TAT at the C-terminus of VIP was constructed and prepared using intein mediated purification with an affinity chitin-binding tag (IMPACT) system to enhance the brain uptake efficiency for the medical application in central nervous system. It was found by labeling VIP-TAT and VIP with fluorescein isothiocyanate (FITC) that the extension with TAT increased the brain uptake efficiency of VIP-TAT significantly. Then short-term and long-term treatment with scopolamine (Scop) was used to evaluate the effect of VIP-TAT or VIP on Scop induced amnesia. Both short-term and long-term administration of VIP-TAT inhibited the latent time reduction in step-through test induced by Scop significantly, but long-term administration of VIP aggravated the Scop induced amnesia. Long-term i.p. injection of VIP-TAT was shown to have positive effect by inhibiting the oxidative damage, apoptosis and the cholinergic system activity reduction that induced by Scop, while VIP exerted negative effect in brain opposite to that in periphery system. The in vitro data showed that VIP-TAT had not only protective but also proliferative effect on Neuro2a cells which was inhibited by PAC1 antagonist PACAP(6-38). Competition binding assay and cAMP assay confirmed that VIP-TAT had higher affinity and activation for PAC1 than VIP. So it was concluded that the significantly stronger protective effect of VIP-TAT against Scop induced amnesia than VIP was due to (1) the enhanced brain uptake efficiency of VIP-TAT and (2) the increased affinity and activation of VIP-TAT for receptor PAC1.
Keywords: VIP-TAT; Scopolamine; Amnesia; Neuro2a; PAC1;
Serum irisin levels and thyroid function—Newly discovered association by Marek Ruchala; Ariadna Zybek; Ewelina Szczepanek-Parulska (51-55).
Irisin is a newly discovered adipo-myokin, which is reported to have a significant influence on the body metabolism and thermogenesis. Other influencing factors on metabolic state are thyroid hormones, which increase heat production and control the energy balance. Due to numerous similarities in action it seems imperative to explore these substances’ potential mutual influence on the body. The aim of the study is to provide the first ever, according to our knowledge, evaluation of serum irisin concentrations in patients with thyroid dysfunction and its correlation with creatine kinase (CK) levels – a serum marker of muscle damage. The studied group consisted of 20 patients with newly diagnosed thyroid disorder – hyperthyroidism or hypothyroidism. Venous blood samples were analyzed for irisin, thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and CK serum concentrations. Patients’ body mass index (BMI), body weight and muscle mass were evaluated using bioelectrical impedance analysis (BIA). Median serum irisin levels were lower in hypothyroid (117.30 ng/ml) than hyperthyroid (161.95 ng/ml) patients with a borderline statistical significance (p = 0.0726). The negative correlation between irisin and TSH levels was demonstrated (r = −0.4924, p = 0.0230), as well as the positive correlation between irisin and FT4 levels (r = 0.4833, p = 0.0360). The CK level was negatively correlated with irisin, FT4 and FT3 concentrations (r = −0.7272, p = 0.0140; r = −0.9636, p = <0.0001; r = −0.8838, p = 0.0007, respectively). The study demonstrates that irisin concentrations may vary according to the thyrometabolic state, which potentially could be related to the degree of muscle damage.
Keywords: Irisin; Thyroid function; Hyperthyroidism; Hypothyroidism;
Proteomic white adipose tissue analysis of obese mice fed with a high-fat diet and treated with oral angiotensin-(1–7) by João Marcus Oliveira Andrade; Fernanda de Oliveira Lemos; Simone da Fonseca Pires; Ruben Dario Sinisterra Millán; Frederico Barros de Sousa; André Luiz Sena Guimarães; Mahboob Qureshi; John David Feltenberger; Alfredo Maurício Batista de Paula; Jaime Tolentino Miranda Neto; Miriam Teresa Paz Lopes; Hélida Monteiro de Andrade; Robson Augusto Souza Santos; Sérgio Henrique Sousa Santos (56-62).
Angiotensin-(1–7) has been described as a new potential therapeutic tool for the treatment and prevention of metabolic disorders by regulating several pathways in visceral white adipose tissue (vWAT). The aim of this study was to access the proteins differentially regulated by Ang-(1–7) using proteomic analysis of visceral adipose tissue. Male mice were divided into three groups and fed for 60 days, with each group receiving one of the following diets: standard diet + HPβCD (ST), high fat diet + HPβCD (HFD) and high fat diet + Ang-(1–7)/HPβCD (HFD + Ang-(1–7)). Body weight, fat weight and food intake were measured. At the end of treatment, Ang-(1–7) induced a decrease in body and fat weight. Differential proteomic analysis using two-dimensional electrophoresis (2-DE) combined with mass spectrometry were performed. Results of protein mapping of mesenteric adipose tissue using 2-DE revealed the presence of about 450 spots in each gel (n = 3/treatment) with great reproducibility (>70%). Image analysis and further statistical analysis allowed the detection and identification of eight proteins whose expression was modulated in response to HFD when compared to ST. Among these, two proteins showed a sensitive response to Ang-(1–7) treatment (eno1 and aldehyde dehydrogenase). In addition, three proteins were expressed statistically different between HFD + Ang-(1–7) and HFD groups, and four proteins were modulated compared to standard diet. In conclusion, comparative proteomic analysis of a mice model of diet-induced obesity allowed us to outline possible pathways involved in the response to Ang-(1–7), suggesting that Ang-(1–7) may be a useful tool for the treatment of metabolic disorders.
Keywords: Renin–angiotensin system; Ang-(1–7); Obesity; Metabolism; Proteomic;
Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: A positive role for peptide dehalogenation by Emily B. Martin; Stephen J. Kennel; Tina Richey; Craig Wooliver; Dustin Osborne; Angela Williams; Alan Stuckey; Jonathan S. Wall (63-70).
Dynamic molecular imaging provides bio-kinetic data that is used to characterize novel radiolabeled tracers for the detection of disease. Amyloidosis is a rare protein misfolding disease that can affect many organs. It is characterized by extracellular deposits composed principally of fibrillar proteins and hypersulfated proteoglycans. We have previously described a peptide, p5, which binds preferentially to amyloid deposits in a murine model of reactive (AA) amyloidosis. We have determined the whole body distribution of amyloid by molecular imaging techniques using radioiodinated p5. The loss of radioiodide from imaging probes due to enzymatic reaction has plagued the use of radioiodinated peptides and antibodies. Therefore, we studied iodine-124-labeled p5 by using dynamic PET imaging of both amyloid-laden and healthy mice to assess the rates of amyloid binding, the relevance of dehalogenation and the fate of the radiolabeled peptide. Rates of blood pool clearance, tissue accumulation and dehalogenation of the peptide were estimated from the images. Comparisons of these properties between the amyloid-laden and healthy mice provided kinetic profiles whose differences may prove to be indicative of the disease state. Additionally, we performed longitudinal SPECT/CT imaging with iodine-125-labeled p5 up to 72 h post injection to determine the stability of the radioiodinated peptide when bound to the extracellular amyloid. Our data show that amyloid-associated peptide, in contrast to the unbound peptide, is resistant to dehalogenation resulting in enhanced amyloid-specific imaging. These data further support the utility of this peptide for detecting amyloidosis and monitoring potential therapeutic strategies in patients.
Keywords: Amyloid imaging; Peptide radiotracer; Dynamic PET imaging; SPECT; Dehalogenation;
A tagged parathyroid hormone derivative as a carrier of antibody cargoes transported by the G protein coupled PTH1 receptor by Xavier Charest-Morin; Jean-Philippe Fortin; Robert Lodge; Isabelle Allaeys; Patrice E. Poubelle; François Marceau (71-79).
Based on the known fact that the parathyroid hormone (PTH) might be extended at its C-terminus with biotechnological protein cargoes, a vector directing the secretion of PTH1–84 C-terminally fused with the antigenic epitope myc (PTH-myc) was exploited. The functional properties and potential of this analog for imaging PTH1R-expressing cells were examined. The PTH-myc construct was recombinantly produced as a conditioned medium (CM) of transfected HEK 293a cells (typical concentrations of 187 nM estimated with ELISAs for PTH). PTH-myc CM induced cyclic AMP formations (10 min), with a minor loss of potency relative to authentic PTH1–84, and c-Fos expression (1–3 h). Treatment of recipient HEK 293a cells transiently expressing PTH1R with PTH-myc CM (supplemented with a fluorescent monoclonal anti-myc tag antibody, either 4A6 or 9E10) allowed the labeling of endosomal structures positive for Rab5 and/or for β-arrestin1 (microscopy, cytofluorometry). Authentic PTH was inactive in this respect, ruling out a non-specific form of endocytosis like pinocytosis. Using a horseradish peroxidase-conjugated secondary antibody, the endocytosis of the PTH-myc-based antibody complex by endogenous PTH1R was evidenced in MG-63 osteoblastoid cells. The secreted construct PTH-myc represents a bona fide agonist that supports the feasibility of transporting cargoes of considerable molecular weight inside cells using arrestin and Rab5-mediated PTH1R endocytosis. PTH-myc is also transported into cells that express PTH1R at a physiological level. Such tagged peptide hormones may be part of a cancer chemotherapy scheme exploiting a modular cytotoxic secondary antibody and the receptor repertoire expressed in a given tumor.
Keywords: Parathyroid hormone; PTH1 receptor; Osteoblast; Receptor-mediated transport;
Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary by Virginia M. Pereira; Kinulpe Honorato-Sampaio; Almir S. Martins; Fernando M. Reis; Adelina M. Reis (80-85).
Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2 mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries.
Keywords: Atrial natriuretic peptide; Ovary; Steroidogenesis; Polycystic ovaries;
Increased acyl ghrelin but decreased total ghrelin and unacyl ghrelin in Chinese Han people with impaired fasting glucose combined with impaired glucose tolerance by Li Huang; Yuzhen Tong; Fang Zhang; Qiu Yang; Daigang Li; Shugui Xie; Yi Li; Hongyi Cao; Lizhi Tang; Xiangxun Zhang; Nanwei Tong (86-94).
We assessed the plasma acyl ghrelin (AG), unacyl ghrelin (UAG), and total ghrelin (TGhr) levels in Chinese adults with pre-diabetes and newly diagnosed diabetes mellitus (NDDM) after an oral glucose tolerance test (OGTT), and abdominal subcutaneous fat area and visceral fat area (VFA) were measured. Fasting AG level was increased in the impaired fasting glucose (IFG) combined with impaired glucose tolerance (IFG + IGT) and NDDM groups. AG, UAG, and TGhr levels were significantly decreased post-OGTT, and the decrements of 30-min AG, UAG, and TGhr post-OGTT were not significantly different among groups. UAG and TGhr levels did not differ significantly among the normal glucose tolerance (NGT), IFG and NDDM groups, but they decreased obviously in the IFG + IGT and impaired glucose tolerance (IGT) groups. The NDDM group had larger VFA than the NGT, IGT, and IFG + IGT groups, even after adjustment for height, it was still larger than the NGT group. The factors such as dyslipidemia and obesity which are prone to develop insulin resistance (IR) and decrease insulin sensitivity (IS) were negatively correlated with UAG and TGhr, positively with AG/UAG, while no correlations with AG. In terms of evaluating IS and IR, AG/UAG ratio may be superior in AG concentration. Our findings suggest that relative sufficiency of AG, the deficiency of TGhr and UAG are already present in IFG + IGT patients. We speculate that there is UAG resistance in severe hyperglycemia (diabetic state), which could produce elevated TGhr and UAG compared to IFG + IGT group. In the development of T2D, increase of VFA could be the initiating factor, leading elevated AG, reduced UAG, IR, decreased IS, and finally hyperglycemia.
Keywords: Visceral fat area; Acyl ghrelin; Insulin resistance; Newly diagnosed diabetes mellitus; Pre-diabetes;
Ablation of glucagon receptor signaling by peptide-based glucagon antagonists improves glucose tolerance in high fat fed mice by Laura M. McShane; Zara J. Franklin; Finbarr P.M. O’Harte; Nigel Irwin (95-101).
Modification to the structure of glucagon has provided a number of glucagon receptor antagonists with possible therapeutic application for diabetes. These novel peptide analogs include desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon. This study has evaluated the metabolic benefits of once daily administration of desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon in high fat (45%) fed mice for 15 days. Administration of desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon had no significant effect on body weight, food intake or circulating glucose concentrations during the treatment period. However, both peptides significantly (P < 0.05 to P < 0.01) reduced circulating plasma insulin concentrations from day 6 onwards. Oral glucose tolerance and insulin sensitivity, as assessed by exogenous insulin administration, were significantly (P < 0.01 to P < 0.001) improved by both desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon. These metabolic benefits were accompanied by significantly (P < 0.01) increased pancreatic insulin stores. No significant differences in blood triacylglycerol or cholesterol levels were noted with desHis1Pro4Glu9-glucagon, however desHis1Pro4Glu9(Lys30PAL)-glucagon treatment significantly (P < 0.01) increased HDL-cholesterol levels. Glucagon-mediated elevations of glucose and insulin were effectively (P < 0.01 to P < 0.001) annulled in both treatment groups on day 15. Interestingly, glucose levels during an intraperitoneal glucose tolerance test were not altered by either desHis1Pro4Glu9-glucagon or desHis1Pro4Glu9(Lys30PAL)-glucagon treatment. These data provide further evidence that glucagon antagonism could provide an effective means of treating T2DM.
Keywords: Glucagon antagonist; Diabetes; Glucose tolerance; Insulin sensitivity;
Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: New potential treatment of abdominal pain associated with inflammatory bowel diseases by Marta Sobczak; Andrzej Pilarczyk; Mateusz Jonakowski; Agata Jarmuż; Maciej Sałaga; Andrzej W. Lipkowski; Jakub Fichna (102-106).
Biphalin, a mixed MOP/DOP agonist, displays a potent antinociceptive activity in numerous animal models of pain. The aim of the study was to characterize the anti-inflammatory and antinociceptive action of biphalin in the mouse models of colitis. The anti-inflammatory effect of biphalin (5 mg/kg, twice daily, i.c. and i.p.) was characterized in a semi-chronic mouse model of colitis, induced by i.c. injection of trinitrobenzenesulfonic acid (TNBS). The antinociceptive action of biphalin (5 mg/kg, i.p. and i.c.) in inflamed mice was assessed in mustard oil-induced model of visceral pain and in the hot plate test. In the semi-chronic mouse model of colitis, biphalin i.c. (5 mg/kg), but not i.p. improved colitis macroscopic score (2.88 ± 0.19 and 4.99 ± 0.80 units for biphalin and vehicle treated animals, respectively). Biphalin injected i.p. and i.c. (5 mg/kg) displayed a potent antinociceptive action in the mustard oil-induced pain test. In the hot plate test, biphalin (5 mg/kg, i.p.) produced a potent antinociceptive activity in inflamed mice, suggesting central site of action. Our data suggest that biphalin may become a novel opioid-based analgesic agent in IBD therapy and warrant further investigation of its pharmacological profile.
Keywords: Biphalin; Inflammatory bowel diseases; Inflammatory pain; Mixed opioid agonist; Opioid receptors;