Modulation of Autophagy Signal Pathway in Type 2 Diabetes Mellitus Rat Model Using Phytochemical Extracts

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sanaa Eissa Mohamed ◽  
Amany Helmy Mohamed ◽  
Meram Mohamed Bekhit ◽  
Maha Saad Zenhom Sayed
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Cerna Network ◽  
Type 2 Dm

Abstract Background Type 2 DM is a chronic metabolic disease characterized by insulin resistance and beta cell dysfunction. It is an extremely heterogeneous disease in which the insulin resistance and beta cell dysfunction resulted from environmental and genetic factor. Type 2 diabetes is the most prevalent form of diabetes worldwide and account for 90% of cases globally. It represents a major public health threat and considered as a principal cause of morbidity and mortality affecting almost 6% of the world’s population. Patients with type 2 diabetes usually have insulin resistance and relative insulin deficiency and are often associated with a strong genetic predisposition. Objective To retrieve potential miRNA-associated ceRNAs Linked to autophagy, insulin resistance and type 2 DM from Public microarray databases followed by validation of the chosen network in animal model. To evaluate the efficacy of Isorhamentin as a potential therapeutic strategy to modulate the autophagy pathway and IR in type 2 DM. Patients and Methods This study was done at Medical Biochemistry Department, Faculty of Medicine, Ain Shams University during the period from December 2019 – June 2020 and included 50 wistar male rats. 50 Male Wistar rats weighed (140-150g), age nearly two months, were purchased from the Holding Company for Biological Products and Vaccines. They were acclimatized to laboratory environment for at least one week with free access to water and food before induction of diabetes. Experiment for eight weeks duration was planned after a pilot study was performed for determination of the most effective and least toxic STZ dose. Results Our study demonstrated that “Isorhamentin” can be potential treatment in type 2 diabetes mellitus through modulation of Autophagy signaling pathway related genes and ceRNA network. Isorhamentin down-regulates the expression of m-tor mRNA and it up-regulates the expression of miR-1. Conclusion The results of our study Support our previous hypothesis that miR-1 miRNA and mTOR mRNA act as ceRNA network and might play an important role in the pathogenesis of autophagy and insulin resistance and T2DM.And could be potential therapeutic target by isorhamentin to modulate the expression of the deregulated network in type 2 DM.

scholarly journals Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population

2013 ◽  
Vol 16 (4) ◽  
pp. 17-22 ◽  
Author(s):  
Irina Arkad'evna Bondar' ◽  
Maksim Leonidovich Filipenko ◽  
Olesya Yur'evna Shabel'nikova ◽  
Ekaterina Alexandrovna Sokolova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Allelic Frequency ◽  
Beta Cell Dysfunction ◽  
Tcf7l2 Gene ◽  
Cell Dysfunction

Aim.  To investigate the association of polymorphisms in TCF7L2 and PPARG2 genes with type 2 diabetes mellitus (T2DM) in Novosibirsk population. Materials and Methods. We examined 391 patients with T2DM and 556 individuals with normal glucose metabolism. Allelic identification was performed with TaqMan technique, implementing allele-specific real-time PCR. Results.  Analysis shows that allelic frequency distribution of rs1801282 variant of PPARG2 gene and rs7903146 variant of TCF7L2 differs significantly between the study and control groups (OR [CI 95%]=1.44 [1.12?1.85], p=0.005 and OR [CI 95%]=1.57 [1.17?2.10], p=0.003, respectively). T2DM patients with T/T genotype of rs7903146 variant of TCF7L2 gene had lower BMI (p=0.02). Observed combination of risk alleles reached 99%. Combined beta-cell dysfunction and insulin resistance genotypes were identified in 56% of tested subjects, isolated insulin resistance ? in 42.2% of subjects, and isolated beta-cell dysfunction ? in 0.8% of subjects. Conclusion.  Our data shows that carrier state of 12Pro rs1801284 variant of PPARG2 gene and T-allele rs7903146 variant of TCF7L2 gene are associated with T2DM in Novosibirsk population, increasing its risk 1.44 and 1.57 times, respectively. Combination of these polymorphisms was observed in 99% of patients with T2DM.

The Arg121Trp variant in PAX4 gene is associated with beta-cell dysfunction in Japanese subjects with type 2 diabetes mellitus

Metabolism ◽  
2006 ◽  
Vol 55 (2) ◽  
pp. 213-216 ◽  
Author(s):  
Yoshiharu Tokuyama ◽  
Kana Matsui ◽  
Toshiharu Ishizuka ◽  
Toru Egashira ◽  
Azuma Kanatsuka
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Japanese Subjects

Comparison of Sleeve Gastrectomy and Conservatory Treatment Effect on Biochemical and Hormonal Profile of Obese Type 2 Diabetes Subjects: CREDOR Randomized Controlled Study Results

2017 ◽  
Vol 68 (7) ◽  
pp. 1622-1627 ◽  
Author(s):  
Diana Simona Stefan ◽  
Andrada Mihai ◽  
Daiana Bajko ◽  
Daniela Lixandru ◽  
Laura Petcu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Beta Cell ◽  
Beta Cell Dysfunction ◽  
Control Group ◽  
Cell Dysfunction ◽  
Randomized Controlled

Metabolic surgery is the most efficacious method for the treatment of morbid obesity and was recently included among the antidiabetes treatments recommended in obese type 2 diabetes (T2D) patients. The aim of this study was to compare in a randomized controlled trial the effect of sleeve gastrectomy (SG) to that of intensive lifestyle intervention plus pharmacologic treatment on some markers of insulin resistance and beta cell function as well as some appetite controlling hormones in a group of male obese T2D subjects. The study groups comprised 20 subjects for SG and 21 control subjects. Fasting blood glucose, insulin, proinsulin, adiponectin, leptin, ghrelin, HOMA-IR, HOMA-%B, proinsulin-to-insulin ratio and proinsulin-to-adiponectin ratio were evaluated at baseline and after one year follow-up. Overall, patients in the SG group lost 78.98% of excess weight loss (%EWL) in comparison with 9.45% in the control group. This was accompanied by a significant improvement of insulin resistance markers, including increase of adiponectin and decrease of HOMA-IR, while no changes were recorded in the control group. Weight loss was also associated with a significant improvement of proinsulin-to-insulin and proinsulin-to-adiponectin ratio, both surrogate markers of beta cell dysfunction. These also improved in the control group, but were only marginally significant. Our findings suggest that improved insulin resistance and decreased beta cell dysfunction after sleeve gastrectomy might explain diabetes remission associated with metabolic surgery.

scholarly journals Correlation Between Lipid Profile with Type 2 Diabetes Mellitus Progression

2020 ◽  
Vol 8 (2) ◽  
pp. 66-72
Author(s):  
Angiesta Pinakesty ◽  
Restu Noor Azizah
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Lipid Profile ◽  
Cholesterol Levels ◽  
Type 2 Dm ◽  
Hba1c Levels

Introduction: Diabetes mellitus (DM) is a non-communicable disease that has increased from year to year. Type 2 diabetes mellitus is not caused by lack of insulin secretion, but is caused by the failure of the body's cells to respond to the hormone insulin (insulin resistance). Insulin resistance was found to be a major contributor to atherogenic dyslipidemia. Dyslipidemia in DM risks 2 to 4 times higher than non-DM. Although dyslipidemia has a great risk for people with type 2 diabetes mellitus, this conventional risk factor only explains a portion (25%) of excess cardiovascular risk in type 2 DM. Discussion: In uncontrolled type 2 DM patients, LDL oxidation occurs faster which results from an increase in chronic blood glucose levels. Glycemic control as a determinant of DM progressivity is determined through HbA1c examination. HbA1c levels are associated with blood triglyceride levels. Meanwhile, triglyceride levels are associated with total cholesterol and HDL cholesterol levels. HbA1c levels are also associated with LDL cholesterol levels. Conclusion: There is a relationship between lipid profile and the progression of type 2 diabetes mellitus.   Keywords: type 2 diabetes mellitus, dyslipidemia, HbA1c, glycemic control, lipid profile

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