Insulin secretory dysfunction is major pathophysiology of diabetes which is aggravated by β-cell apoptosis. Metformin and sulfonylureas, two major oral hypoglycemic agents used for the treatment of diabetes, enhance insulin sensitivity and stimulate insulin secretion, respectively. Though some dipeptidyl peptidase-IV inhibitors are reported for β-cell protective activity; however, results are not conclusive yet. Therefore, taking advantage of our in house pure compounds library an attempt was made to identify compounds having β-cell protective as well as insulin secretory activity, and study their mechanism(s) at molecular and cellular levels. In order to evaluate the compounds for this dual activity, we used pancreatic β-cell line MIN6 cells to develop H2O2 mediated apoptosis and glucose stimulated insulin secretory assay systems. Out of 34 tested compounds, seven (7) compounds showed strong β-cell apoptosis inhibitory activity. Amongst them genestein (GS), quercetin (QCT), and cinnamic acid (CA) were evaluatedthrough triple channel immunostaining for mitochondria-actin-nuclei which revealed restoration of mitochondrial membrane potential, preservation of cytoarchitecture of cells and reduced nuclear condensation in MIN6 cells. Oxidative stress mediated activation of cleaved caspase 3 was undetectable in MIN6 cells after treatment with these compounds, further confirming the inhibition of mitochondria mediated apoptosis. Moreover, real time PCR study of mRNA expression showed that QCT and GS both downregulated the expression of apoptotic gene Casp9, and increased expression of both Ins1 and Ins2 genes. GS, QCT and CA also stimulated insulin secretion from MIN6 cells/ mice isolated islets. We found CA significantly inhibited nuclear condensation, decreased TUNEL positivity of pancreatic β-cells and preserved islets cytoarchitecture in Wistar rats. The effect of nicotinamide-cinnamic acid (NA-CA) was also studied in vivo, and we found that NA-CA significantly decreases β-cell apoptosis and induces insulin secretion than these agents alone. Immunohistochemical analysis of NA-CA pre-treated rat pancreas revealed decreased cleaved casp3 levels and increased phosphorylation of ERK½ in β-cells. Moreover, real time PCR anlaysis of NA-CA showed decrease in expression of Casp3 and Casp9 mRNA in MIN6 cells. This suggests that dual effect of NA-CA seems to be mediated via ERK½ signaling pathway and through modulating the mRNA expressions of apoptotic proteins. Intriguingly, we found orobol, tambulin and hispidulin as novel insulin secretagogues in the current study. TM enhanced insulin secretion in a dose dependent manner only at stimulatory glucose concentration in isolated mice islets. Pharmacological inhibition of protein kinase A and calcium channels significantly decreased insulin secretion induced by TM. This suggests that TM exerts an exclusive insulin secretory effect by modulating Ca2+ channels and PKA pathway. From the current study, some compounds with potent insulin secretory activity were identified. Interestingly few lead compounds having dual activity were also discovered. Taken together, these compounds may serve as lead compounds to be further studied for their anti-diabetic activity.
مولانا محمد اسحاق سندیلوی ندوی مرحوم پاکستان سے یہ افسوسناک خبر بہت تاخیر سے ملی کہ مولانا محمد اسحق سندیلوی ندوی کا نوے ۹۰ سال کی عمر میں انتقال ہوگیا۔ اناﷲ وانا الیہ راجعون۔ مولانا کی تعلیم مدرسہ فرقانیہ اور دارالعلوم ندوۃالعلماء میں ہوئی، عرصہ تک وہ دارالعلوم میں درس و تدریس کے فرائض انجام دیتے رہے، جب مولانا محمد اویس نگرامی ندوی، ندوہ کے شیخ التفسیر تھے اس وقت مولانا سندیلوی شیخ الحدیث تھے اور ان دونوں جید اساتذۂ فن کی موجودگی ندوہ میں قران السعدین کا منظر پیش کرتی تھی، وہ ندوہ کے مہتمم بھی رہے اور وہاں کی مجلس اشاعت اور تحقیقات شرعیہ کے ناظم بھی۔ درس و تدریس کے ساتھ ان کا تصنیفی ذوق اور تحریری مذاق اعلیٰ درجہ کا تھا، تاریخ وفقہ اسلامی پر ان کی نظر وسیع و عمیق تھی، ۱۹۴۷ء سے قبل مسلم لیگ کے ذمہ داروں کو خیال ہوا کہ متوقع اسلامی حکومت کا ایک قانون اساسی، اسلامی تعلیمات کی روشنی میں مرتب کیا جائے تو اس کے لیے یو پی مسلم لیگ نے نظام اسلامی کے نام سے ایک مجلس کی تشکیل کی جس کے ارکان میں مولانا سید سلیمان ندوی، مولانا عبدالماجد دریا بادی، مولانا سید ابوالاعلیٰ مودودی اور مولانا آزاد سبحانی جیسے جید علماء شامل تھے، مجلس کے روح رواں حضرت سید صاحب کی جو ہر شناس نظر اس اسلامی قانون کے خاکہ و دستور کی ترتیب و تیاری کے لیے مولانا اسحق سندیلوی ہی پررکی، جنھوں نے بڑی خوش اسلوبی سے ایک ضخیم کتاب تیار کی جو بعد میں دارالمصنفین سے اسلام کا سیاسی نظام، کے نام سے شایع ہوکر مقبول ہوئی اس میں انہوں نے نظریہ خلافت، قانون، حکومت، خلیفہ، مجلس تشریعی، رعایا، بیت المال، افتا، احتساب، حرب و دفاع، صوبائی حکومتیں، خارجی معاملات پر دور جدید کے سیاق و سباق میں فاضلانہ بحث...
This research is motivated by the ups and downs in the quality of employee performance at PT Enseval Putera Megatrading Pekanbaru Branch from 2020 to 2022. Based on the formulation of the problems that have been made, this study aims to determine the effect of compensation and work environment on employee performance at PT Enseval Putera Megatrading Pekanbaru Branch This research is a type of quantitative research. The sample used in this study were employees of PT Enseval Putera Megatrading Pekanbaru Branch as many as approximately 52 people. Sampling technique by means of Simple Random Sampling. With data collection through observation, interviews, questionnaires and literature studies. The analysis technique in this study uses Multiple Linear Regression Analysis. This study uses multiple linear regression with the help of the SPSS Ver program. 21.00. The results of this study, compensation has a positive effect on employee performance. This is evident from the results of the t test which obtained t count X1 greater than t table, namely the value of t count (7.467) greater than t table (2.010) accepted at a significance level of 5%. The work environment has a positive effect on employee performance. This is evident from the results of the t test which obtained the t count X2 greater than the t table, namely the t value (7.484) greater than the t table (2.010), accepted at the 5% significance level. Compensation and work environment together have a positive effect on employee performance. This is evident from the results of the F test which shows the results of the F count of (415.672) greater than the F table of (3.19) accepted at the 5% significance level. Islamic economic review of the effect of compensation and work environment on employee performance at PT Enseval Putera Megatrading Pekanbaru branch can be categorized as sharia based on ijarah contract.
Experience is a key source of learning. Voluntary services (VS) are one such experiential source to learn and grow from. The present case study used mixed methods (survey tools and in-depth interviews) to explore the perspectives of Ismaili youth on the meaning, value, and educative potentials of their voluntary services based in Karachi. The data was collected from Ismaili youth (18 to 23 years) belonging to three community sites in the city Karachi (Garden, Metroville and Clifton). The study’s data showed that the participants understand the meaning and value of voluntary services in myriad ways, starting from processes of benefiting the lives of the community members, to making a difference in some one’s life, to teaching academic/social subjects and skills to community. Khidmat to the religious leader and to their community appeared as key factors in their involvement in voluntary services. The participants were enrolled in various interconnected institutions and services established by their respective community sites. Even though the volunteers’ learning from their services is not purposefully structured, many participants actively and subtly learnt and developed skills, knowledge and attitudes such as communication, teaching, problem solving, critical thinking, reflecting, presenting, public speaking, time management, multi-tasking, people management, learning about diversity, respect towards others, patience, confidence in their ability, flexibility, leadership, and, most importantly, about justice and diversity. They expressed critical insights about instances of favoritism, nepotism, injustice and unfair treatment of the ‘other’ during their voluntary experiences. The link between academic/school subjects and voluntary experiences was limited to religious education. Overall the youth’s learning from their voluntary services showed the potentials for developing into successful leaders for their community and larger society, with broad vision and relevant skills and dispositions for 21st century. The youth appeared to have deeply thought suggestions, which make them natural partners to the community leaders in making VS more meaningful, relevant, and empowering. Dialogue with the youth can make the link between voluntary services and learning more robust, explicit and mutually beneficial. These transformative potentials can be tapped on, if the community leaders actively listen to their youth voices.