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Reduced pancreatic polypeptide response is associated with early alteration of glycemic control in chronic pancreatitis.

胰多肽反应降低与慢性胰腺炎血糖控制的早期改变相关。

  • 影响因子:3.00
  • DOI:10.1016/j.diabres.2019.107993
  • 作者列表:"Aslam M","Vijayasarathy K","Talukdar R","Sasikala M","Nageshwar Reddy D
  • 发表时间:2020-02-01
Abstract

AIM:To study the incidence of glucose intolerance in CP patients without diabetes by performing oral glucose tolerance test (OGTT). METHODS:We screened consecutive Indian CP patients without diabetes over 6 months by performing OGTT and correlated with physical characteristics and glycated hemoglobin (HbA1c). We also compared c-peptide and pancreatic polypeptide response in different groups based on OGTT. Relevant statistical tests were performed. P < 0.05 was considered significant. RESULTS:Total of 171 patients were screened. Mean duration of CP was 5.03 ± 4.32 years. 55 were detected to have prediabetes and 40 DM on OGTT. CP patients with diabetes and prediabetes had significantly dilated pancreatic duct compared to non-diabetic CP (4.2 ± 2.7 mm, 3.6 ± 2.7 mm, 2.84 ± 2.25 mm; p = 0.018). Fasting blood glucose (FBS) and 2-hour OGTT were 109.35 ± 19.06, 97.47 ± 11.94, 85.24 ± 9.95 and 236.13 ± 31.42, 154.65 ± 19.53, 112.89 ± 16.32 in patients with DM, prediabetes and CP patients without diabetes (p < 0.0001). There was a good c-peptide response (p = 0.001) and reduced pancreatic polypeptide response (p = 0.003) in CP patients compared to controls. CONCLUSION:Early in the course of disease reduced pancreatic polypeptide response in the presence of good c-peptide response may result in development of DM.

摘要

目的: 通过口服葡萄糖耐量试验 (OGTT) 研究无糖尿病的 CP 患者的葡萄糖耐受不良发生率。 方法: 我们通过 OGTT 筛查连续 6 个月以上无糖尿病的印度 CP 患者,并与身体特征和糖化血红蛋白 (HbA1c) 相关。我们还根据 OGTT 比较了不同组的 c肽和胰多肽反应。进行相关统计检验。P

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发表时间:2020-01-27
来源期刊:Aging
DOI:10.18632/aging.102776
作者列表:["Akula SM","Ruvolo PP","McCubrey JA"]

METHODS::Pancreatic ductal adenocarcinoma (PDAC) is a disease of aging. The TP53 gene product regulates cell growth, aging, and cancer. To determine the important targets of TP53 in PDAC, we examined the expression of 440 proteins on a reverse phase protein array (RPPA) in PDAC-derived MIA-PaCa-2 cells which either had WT-TP53 or lacked WT-TP53. MIA-PaCa-2 cells have a TP53 mutation as well as mutant KRAS and represent a good in vitro model to study PDAC. RPPA analysis demonstrated expression of tumor promoting proteins in cells that lacked WT-TP53; and this feature could be reversed significantly when the cells were transfected with vector encoding WT-TP53 or treated with berberine or a modified berberine (BBR). Expression of miR-34a-associated signaling was elevated in cells expressing WT-TP53 compared to cells expressing mTP53. Results from in vivo studies using human PDAC specimens confirmed the in vitro results as the expression of miR-34a and associated signaling was significantly decreased in PDAC specimens compared to non-cancerous tissues. This study determined SERPINE1 as a miR-34a target with relevance to the biology of PDAC. Thus, we have identified a key target (SERPINE1) of the TP53/miR-34a axis that may serve as a potential biomarker for early detection of pancreatic cancer.

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影响因子:5.13
发表时间:2020-01-28
DOI:10.1080/17425247.2020.1723544
作者列表:["Kou L","Huang H","Lin X","Jiang X","Bao S","Luo Q","Sun J","Yao Q","Ganapathy V","Chen R"]

METHODS::Background: SLC6A14 (ATB0,+), a Na+/Cl-coupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver cancer.Research design and methods: Here we explored the mechanism of ATB0,+-mediated entry of such liposomes. As ATB0,+ is highly-expressed in pancreatic cancer, we also examined the therapeutic utility of ATB0,+-targeted liposomal drug delivery to treat this cancer.Results: The uptake of lysine-conjugated liposomes (LYS-LPs) was greater in ATB0,+-positive MCF7 cells. The uptake process consisted of two steps: binding and internalization. The binding of LYS-LPs to MCF7 cells was higher than that of bare liposomes, and the process was dependent on Na+ and Cl-, and inhibitable by ATB0,+ substrates or blocker. In contrast, the internalization step was independent of lysine. The cellular entry of LYS-LPs facilitated by ATB0,+ occurred via endocytosis with transient endosomal degradation of ATB0,+ protein with subsequent recovery. Moreover, LYS-LPs also enhanced the uptake and cytotoxicity of gemcitabine in these cells in an ATB0,+-dependent manner.Conclusions: We conclude that ATB0,+ could be exploited for targeted drug delivery in the form of lysine-conjugated liposomes and that the approach represents a novel strategy for enhanced pancreatic cancer therapy.

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影响因子:2.30
发表时间:2020-01-28
DOI:10.1007/s00423-020-01857-4
作者列表:["Okada KI","Kawai M","Hirono S","Kojima F","Tanioka K","Terada M","Miyazawa M","Kitahata Y","Iwahashi Y","Ueno M","Hayami S","Murata SI","Shimokawa T","Yamaue H"]

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