scholarly journals Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jaechan Leem ◽  
Eun Hee Koh

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated withβ-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Zhongmin Alex Ma ◽  
Zhengshan Zhao ◽  
John Turk

Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic isletβ-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor toβ-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS) produced byβ-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead toβ-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reducedβ-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochromecrelease into cytosol and apoptosis. Group VIA phospholipase A2(iPLA2β) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increasesβ-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects onβ-cell mitochondrial phospholipids might prevent or retard development of T2DM.


Author(s):  
Zarish Noreen ◽  
Christopher A. Loffredo ◽  
Attya Bhatti ◽  
Jyothirmai J. Simhadri ◽  
Gail Nunlee-Bland ◽  
...  

The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6, TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling, Type II Diabetes Mellitus Signaling, Apoptosis Signaling, Aryl Hydrocarbon Receptor Signaling, p53 Signaling, Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling, Parkinson’s Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway, Oxidative Phosphorylation, LXR/RXR Activation, and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.


2007 ◽  
Vol 10 (6) ◽  
pp. 698-703 ◽  
Author(s):  
Vera B Schrauwen-Hinderling ◽  
Michael Roden ◽  
M Eline Kooi ◽  
Matthijs KC Hesselink ◽  
Patrick Schrauwen

2020 ◽  
Vol 3 (1) ◽  
pp. 31-45
Author(s):  
Muhammad Sobri Maulana ◽  

Type 2 Diabetes Mellitus or Type 2 DM is a metabolic disease that can cause severe complications so that adequate management which one of the targets is lowering HbA1c level is needed. Up to this time, treatment for Type 2 DM including antihiperglycemic and injection. Herbal remedies as well as dates (Phoenix datcylifera) has been limited even though it has well-known antihyperglycemic effect. To investigate the effectivity of Dates (Phoenix dactylifera) in lowering HbA1c level among Type 2 Diabetes Mellitus patients. Literature searching was conducted on four online databases which are PubMed, Scopus, EBSCO, and Cochrane Library based on inclusion and exclusion criterias. Based on the results of critical studies, seven studies have shown that there is effectiveness in the administration of Dates (Phoenix dactylifera) in patients with type 2 diabetes mellitus on Lowering HbA1c levels and restricition of date diet needed for type 2 diabetes mellitus patients in 3 dates per day that are statistically significant for lowering HbA1c level with value of NNT is 1. Administration of Dates (Phoenix dactylifera) can be used as an adjuvant therapy on Type 2 Diabetes mellitus patients


2020 ◽  
Vol 8 (2) ◽  
pp. 66-72
Author(s):  
Angiesta Pinakesty ◽  
Restu Noor Azizah

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


2020 ◽  
pp. 10-11
Author(s):  
Ravindra Kumar Das ◽  
Rahul Kumar Sinha ◽  
Debarshi Jana

Background: Type 2 diabetes mellitus (DM) is a progressive chronic disorder and sustained control of plasma glucose is essential to prevent complications. Pioglitazoneofthiazolidinedionesand sitagliptin of Dipeptidyl peptidase-4 inhibitors (DPP4I) have recently been used as add-on therapy to control type 2 DM. The aim of this study was to compare the plasma glucose and glycocelatedHb% level of both the group who had poor glycemic control with Metformin and sulfonylurea. MATERIAL AND METHODS: In this observational cohort study, 100 patients with uncontrolled type 2 DM on 2000 mg/day of Metformin and 4 mg/day of Glimepiride were enrolled. The patients were randomly allocated into two groups with fifty each. One group received two divided doses of pioglitazone (30 mg/day) and the other received two divided doses of sitagliptin (100 mg/day) as the third medication. Plasma glucose fasting and 2 hours after drug and meal along with HbA1c were assessed before and after three months of treatment. Results: Fasting plasma glucose level in the sitagliptin group was higher than the pioglitazone group; however, this difference was not statistically significant (130.30 ± 30.29 versus 124.58 ± 46.84, p=0.212). Significantdifferences were not observed in HbA1c (7.20±0.96 versus 7.43±0.99, p=0.563) and plasma glucose 2 hours after meal (194.56±66.22 versus 198.58±51.5, p=0.946) after treatment withsitagliptin and pioglitazone among the two groups. Mean weight in the sitagliptin group was lower compared to the pioglitazone group after treatment, however, this difference was not statistically significant (p=0.824). Conclusion: Both the molecule as third agent had similar efficacy in glycemic control. Sitagliptin is better choice to add-on therapy in obese overweight patients.


2019 ◽  
Vol 09 (03) ◽  
pp. 232-236
Author(s):  
Shabzain Ishrat ◽  
Talea Hoor ◽  
Mohammed Sajid Abbas Jaffri

Type 2 diabetes mellitus (DM) is a chronic disease which deteriorates the quality of life with time. Type 2 DM accounts for more than 90% cases of diabetes mellitus as compared to other types of this disease. There is significant oxidative stress in type 2 DM which plays an important role in the pathogenesis of disease. In order to combat this oxidative stress antioxidant supplements have to be added as add on therapy along with treatment of type 2 DM. Vitamin C is the safest antioxidant which plays significant role in diminishing the oxidative stress. The vitamin C supplementation have good control of FBS and HbA1c and therefore helps in achieving better glycemic control along with prevention of lipid abnormalities.


2016 ◽  
Vol 50 (3) ◽  
pp. 127-131 ◽  
Author(s):  
M Bhanukumar ◽  
Prasanna KH Ramaswamy ◽  
Naveen K Peddi ◽  
Vineetha B Menon

ABSTRACT Aims The objective of the study was to determine the mean platelet volume (MPV) and platelet distribution width (PDW) in subjects with type 2 diabetes mellitus (type 2 DM) compared to subjects without type 2 DM and their correlation with fasting blood glucose, glycosylated hemoglobin (HbA1c), and duration of type 2 DM respectively. Materials and methods A prospective analytical case—control study was conducted involving 50 subjects with type 2 DM and 50 subjects without type 2 DM. The mean and standard deviation were estimated for both the groups separately and independent Student's “t”-test was used for evaluating the significant difference. The statistical evaluation was carried out at 95% confidence level. Results Mean MPV and PDW in case group was significantly higher compared to control group (p < 0.005). Fasting blood glucose, HbA1c, and duration of type 2 DM did not significantly alter MPV or PDW. Conclusion The study concludes that MPV and PDW are significantly increased in patients with type 2 DM compared to patients without type 2 DM. Platelet volume indices are an important, simple, and cost-effective tool that should be used and explored extensively, especially in countries, such as India, for predicting the possibility of impending acute vascular events in patients with type 2 DM. Clinical significance This analytical method helps us to use MPV and PDW as early markers of vascular thrombosis. How to cite this article Bhanukumar M, Ramaswamy PKH, Peddi NK, Menon VB. Mean Platelet Volume and Platelet Distribution Width as Markers of Vascular Thrombosis in Type 2 Diabetes Mellitus. J Postgrad Med Edu Res 2016;50(3):127-131.


2021 ◽  
Vol 2 (1) ◽  
pp. 23-28
Author(s):  
Alexander Petra Sihite ◽  
I Gusti Ngurah Pramesemara ◽  
I Wayan Surudarma

Background: Type 2 diabetes mellitus is a metabolic disease that characterized by high blood sugar levels. This condition is often not noticed immediately and usually patient starting to realize it when complications have been occurred. A long-term complication of type 2 DM that occurred in men is erectile dysfunction (ED). ED is a condition when a person is unable to achieve or maintain an erection for sexual intercourse. One factor that influence the occurrence of ED and its severity in type 2 DM patients is the duration of the disease. Objective: The aim of this study was to determine the relationship of type 2 DM duration and the occurrence of ED. Methods: This study is an observational analytic cross-sectional study conducted at the Puskesmas (Public Health Center) Denpasar Barat I. The research data was obtained through medical record data and fill the International Index of Erectile Function (IIEF-5) questionnaire on 36 type 2 DM patients aged around 40-60 years. The statistical analysis used was Fisher's exact test. Results: The results showed that of the 36 samples, 19 (52.8%) samples had type 2 DM <24 months and 17 (47.2%) samples had type 2 DM >24 months. It was found that 5 (13.9%) samples did not experience ED while the rest experienced ED with different severity. There was a significant relationship between the type 2 DM duration and the occurrence of erectile dysfunction at Puskesmas Denpasar Barat I (p = 0.022). Conclusion: Study has found that type 2 DM patients with the longer duration (>24 months)  have a higher occurrence of ED and tended to be more severe compared to those with shorter duration (<24 months). Further studies should be performed with higher number of patients and more controlled risk factor so it will be more accurate in determining the relationship between the duration of type 2 DM and ED.


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