scholarly journals Treatment with Mammalian Ste-20-like Kinase 1/2 (MST1/2) Inhibitor XMU-MP-1 Improves Glucose Tolerance in Streptozotocin-Induced Diabetes Mice

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4381
Author(s):  
Zakiyatul Faizah ◽  
Bella Amanda ◽  
Faisal Yusuf Ashari ◽  
Efta Triastuti ◽  
Rebecca Oxtoby ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Diabetic Mice ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
In Vivo Models ◽  
Type 2 Dm ◽  
Type 1 Dm

Diabetes mellitus (DM) is one of the major causes of death in the world. There are two types of DM—type 1 DM and type 2 DM. Type 1 DM can only be treated by insulin injection whereas type 2 DM is commonly treated using anti-hyperglycemic agents. Despite its effectiveness in controlling blood glucose level, this therapeutic approach is not able to reduce the decline in the number of functional pancreatic β cells. MST1 is a strong pro-apoptotic kinase that is expressed in pancreatic β cells. It induces β cell death and impairs insulin secretion. Recently, a potent and specific inhibitor for MST1, called XMU-MP-1, was identified and characterized. We hypothesized that treatment with XMU-MP-1 would produce beneficial effects by improving the survival and function of the pancreatic β cells. We used INS-1 cells and STZ-induced diabetic mice as in vitro and in vivo models to test the effect of XMU-MP-1 treatment. We found that XMU-MP-1 inhibited MST1/2 activity in INS-1 cells. Moreover, treatment with XMU-MP-1 produced a beneficial effect in improving glucose tolerance in the STZ-induced diabetic mouse model. Histological analysis indicated that XMU-MP-1 increased the number of pancreatic β cells and enhanced Langerhans islet area in the severe diabetic mice. Overall, this study showed that MST1 could become a promising therapeutic target for diabetes mellitus.

scholarly journals A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Ting Chang ◽  
Liang-Yu Lin ◽  
Jaw-Wen Chen
Keyword(s):  
Insulin Resistance ◽  
Blood Sugar ◽  
Islet Cell ◽  
Diabetic Mice ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Type 2 Dm ◽  
Tnf Α

Systemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 & type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell proliferation and decreased pancreatic interleukin (IL)-6 expression. In the type 2 diabetes and metabolic syndrome models, CCL4 inhibition retarded the progression of hyperglycemia, reduced serum tumor necrosis factor (TNF)-α and IL-6 levels, and improved insulin resistance via reducing the phosphorylation of insulin receptor substrate-1 in skeletal muscle and liver tissues. CCL4 inhibition directly protected pancreatic β-cells from streptozotocin stimulation. Furthermore, CCL4-induced IL-6 and TNF-α expressions could be abolished by siRNA of CCR2/CCR5. In summary, direct inhibition of CCL4 protected pancreatic islet cells, improved insulin resistance and retarded the progression of hyperglycemia in different experimental models, suggesting the critical role of CCL4-related inflammation in the progression of DM. Future experiments may investigate if CCL4 could be a potential target for blood sugar control in clinical DM.

Substance P preserves pancreatic β-cells in type 1 and type 2 diabetic mice

2018 ◽  
Vol 499 (4) ◽  
pp. 960-966 ◽  
Author(s):  
Jihyun Um ◽  
Nunggum Jung ◽  
Dongjin Kim ◽  
Sanghyuk Choi ◽  
Sang-Ho Lee ◽  
...  
Keyword(s):  
Substance P ◽  
Diabetic Mice ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Type 2 Diabetic

Associations between Diabetes Mellitus and Nontuberculous Mycobacterium-Caused Diseases in Taiwan: A Nationwide Cohort Study

2021 ◽  
Author(s):  
Jui-Yang Wang ◽  
Hsin-Chung Lin ◽  
Hsin-An Lin ◽  
Chi-Hsiang Chung ◽  
Lih-Chyang Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Risk ◽  
Cox Regression ◽  
Nontuberculous Mycobacterium ◽  
Research Database ◽  
Cox Regression Analysis ◽  
Type 2 Dm ◽  
Type 1 Dm

Patients with diabetes mellitus (DM) are at greater risk of developing active tuberculosis and other intracellular bacterial infections, although the risk of acquiring infections from nontuberculous Mycobacterium (NTM) remains undefined. This study evaluated associations between DM and incidence of NTM infection-caused pulmonary and cutaneous diseases. Data for DM patients were extracted from the National Health Insurance Research Database of Taiwan. The DM cohort included 136,736 patients, and cases were matched randomly by age, gender, and index year with non-DM patients. Multivariate Cox proportional hazards regression was used to calculate adjusted hazard ratios of incident NTM-caused diseases in the DM cohort compared with non-DM control subjects. The frequency of incident NTM-caused diseases was significantly greater in DM patients (0.12%) than in non-DM patients (0.08%) (P < 0.05), including patients with type 1 DM (0.12%) and type 2 DM (0.12%) (all P < 0.05). Adjusted multivariate Cox regression analysis revealed that the incidence of NTM-caused diseases in DM patients was 1.43-fold greater than that in non-DM patients overall (P < 0.05), particularly in pulmonary (1.13-fold), other specific (excluding pulmonary, cutaneous, and disseminated diseases; 3.88-fold), and unspecific (atypical NTM infection; 1.54-fold) diseases (all P < 0.05). In conclusion, both type 1 DM and type 2 DM patients have high risk of NTM-caused diseases, suggesting that physicians need to pay more attention to this issue concerning the high risk of NTM-caused infection in DM patients.

scholarly journals Activation of CD4+ and CD8+ T-lymphocytes by insulin and GAD in patients with type 1 or 2 diabetes mellitus

2017 ◽  
Vol 6 (8) ◽  
pp. 758-765 ◽  
Author(s):  
Borros Arneth
Keyword(s):  
Diabetes Mellitus ◽  
T Lymphocytes ◽  
Whole Blood ◽  
Blood Samples ◽  
Cd8 T Lymphocytes ◽  
Type 2 Dm ◽  
Whole Blood Samples ◽  
Type 1 Dm

Background The origin of autoimmune disease type 1 diabetes is still unknown. Aim This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. Materials and methods The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers. Results Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects. Discussion These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients. Conclusion These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.

scholarly journals Helicobacter pyloriInfection Is Associated with Type 2 Diabetes, Not Type 1 Diabetes: An Updated Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Jun-Zhen Li ◽  
Jie-Yao Li ◽  
Ting-Feng Wu ◽  
Ji-Hao Xu ◽  
Can-Ze Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Knowledge Database ◽  
Type 2 Dm ◽  
The Difference ◽  
H Pylori ◽  
Type 1 Dm

Background. Extragastric manifestations ofHelicobacter pylori(H. pylori) infection have been reported in many diseases. However, there are still controversies about whetherH. pyloriinfection is associated with diabetes mellitus (DM). This study was aimed at answering the question.Methods. A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reportingH. pyloriinfection in both DM and non-DM individuals were recruited.Results. 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence ofH. pyloriinfection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69,P<0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77–1.96,P=0.38).Conclusion. Our meta-analysis suggested that there is significantly higher prevalence ofH. pyloriinfection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.

scholarly journals Study of cutaneous manifestations of type 2 diabetes mellitus

2018 ◽  
Vol 4 (1) ◽  
pp. 8
Author(s):  
Yoganand J. Phulari ◽  
Vidisha Kaushik
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Age Group ◽  
Cutaneous Manifestations ◽  
Skin Manifestations ◽  
Type 2 Dm ◽  
Type 1 Dm

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Poorly controlled Type 2 diabetes mellitus (DM) is associated with several disorders and microvascular, macrovascular and neuropathic complications. Multiple factors play a role in the manifestations of cutaneous signs of DM. The prevalence of a cutaneous disorder appears to be similar between Type 1 DM and Type 2 DM patients, but Type 2 DM patients develop more frequent cutaneous infections, and Type 1 DM patients manifest more autoimmune-type  cutaneous lesions. The objective of the study was to assess the various cutaneous manifestations of Type 2 DM and the relation of cutaneous manifestations with the duration of Type 2 DM.</span></p><p class="abstract"><strong>Methods:</strong> All patients of Type 2 DM, of age group 20 and above, of both sexes, attending   OPD or IPD at Dr. D. Y. Patil  Hospital, Kolhapur  willing to give written informed consent, were included for the study between August 2014 – July 2016. Complete history and examination of all the patients with regards to onset of cutaneous manifestations was taken.<strong></strong></p><p class="abstract"><strong>Results:</strong> Majority (49%) of respondents were in the age group of 41 to 60 years, and majority (66%) were males. 57.5% were new cases and 42.5% were known cases. Duration of illness- majority 50.58% were &lt;5 years, 27.05% in 6 to 10 years. In present study there were 61% who had infectious skin manifestations and 39% who had non-infectious skin manifestations. Out of infectious manifestations 39.5% had fungal infection<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions:</strong> Therefore on the basis of present study, we conclude that the skin is involved in DM quite often. The manifestations are numerous and varied and many a times they can serve as diagnostic marker for underlying DM. Whenever patients present with multiple skin manifestations, their diabetic status should be checked. The recognition of these skin findings is the key to treatment and prevention<span lang="EN-IN">.</span></p>

scholarly journals Relationship between TP53 and interleukin-6 gene variants and the risk of types 1 and 2 diabetes mellitus development in the Kermanshah province

2021 ◽  
Vol 14 (1) ◽  
pp. 37-44
Author(s):  
Lida Haghnazari ◽  
◽  
Ramin Sabzi ◽  
◽  
Keyword(s):  
Diabetes Mellitus ◽  
Tp53 Gene ◽  
Control Group ◽  
Control Groups ◽  
Codon 72 ◽  
Type 2 Dm ◽  
And Control ◽  
Type 1 Dm

Diabetes mellitus (DM) is a metabolic disorder that results from insufficient secretion or insulin resistance, or both. Insulin secretion deficiency leads to chronic hyperglycemia along with impaired metabolism of proteins, lipids, and carbohydrates. This study aimed to investigate the TP53 gene SNP (single nucleotide polymorphism) rs1042522 genotype and the interleukin-6 (IL-6) gene SNP rs1800795 genotype in DM and control groups. This study was performed on 70 patients with type 1 DM, 100 patients with type 2 DM without related complications, 66 control subjects for type 1 DM, and 95 control subjects for type 2 DM. The control groups were matched regarding age and gender and did not have a familial relationship with the patient groups. All the subjects were residents of Kermanshah, located in the western part of Iran. Polymorphisms of TP53 and IL-6 genes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile, fasting blood glucose, and HbA1c were measured using the ELISA and immunoturbidometric methods. The frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 in type 1 DM and its control group were significantly different (P= 0.013). Likewise, the frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 was significantly different between type 2 DM and control groups (P <0.001). The frequency of genotypes (GG, GC, CC) of G174C polymorphisms in the IL-6 gene was different between type 1 DM and control group as well as between type 2 DM and its control group, but it was not statistically significant. SNP rs1042522 genotypes in the dominant form (CG + GG vs. CC) (OR= 3.880; P < 0.001) and alleles G vs. C alleles (OR= 0.384; P < 0.001) increased the risk of type 2 DM significantly. There was no significant difference between type 1 and type 2 DM groups and respected control groups regarding the frequency of the IL-6 gene SNP rs1800795 alleles. The G allele of SNP rs1042522 encoding the TP53 gene increases the risk of developing DM in the population of the Kermanshah province, Iran.

scholarly journals Blood concentrations of endothelin, interleukins 6 and 10 in men with diabetes mellitus

2021 ◽  
Vol 17 (4) ◽  
pp. 280-286
Author(s):  
E.V. Luchytskiy ◽  
V.E. Luchytskiy ◽  
G.A. Zubkova ◽  
V.M. Rybalchenko ◽  
I.I. Skladanna
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Correlation Coefficient ◽  
Blood Concentration ◽  
Positive Correlation ◽  
Type 2 Dm ◽  
Type 1 Dm ◽  
Spearman’S Correlation

Background. Pathological activation of cytokines is one of the key links in the pathogenesis of diabetes mellitus (DM) and the development of its complications, in particular from the cardiovascular system. According to the vast majority of researchers, the imbalance of pro- and anti-inflammatory cytokines in patients with diabetes mellitus is a significant risk factor for mortality from cardiovascular disease. The purpose of the study was to determine the concentration of markers of a nonspecific inflammatory response (interleukin (IL) 6 and IL-10) in the blood of men with DM and their association with glycated hemoglobin levels and body mass index. Materials and methods. There were examined 46 men with type 2 DM and 28 men with type 1 DM. According to the results of the analysis of variance of the control group, type 2 DM and type 1 DM had significant differences in some indicators. Results. The correlation analysis of the obtained indicators of interleukin concentration showed that in men with type 2 DM under the age of 50 years, the indicators of IL-6 concentration significantly positively correlated with indicators of IL-10 concentration in blood (Spearman’s correlation coefficient 0.562, p < 0.031) and negatively with the duration of diabetes mellitus (Spearman’s correlation coefficient –0.508, p < 0.031). In the group of patients with type 2 DM aged 50 years and older, there was a positive correlation between the blood concentration of IL-6 with the blood concentration of IL-10 (Spearman’s correlation coefficient 0.509, p < 0.031), the blood concentration of IL-10 with glycated hemoglobin levels (Spearman’s correlation coefficient 0.391, p < 0.04) and the duration of diabetes mellitus (Spearman’s correlation coefficient 0.551, p < 0.005). In the group of patients with type 1 DM, there was a positive correlation of IL-6 in the blood with indicators of the blood concentration of IL-10 (Spearman’s correlation coefficient 0.707, p < 0.001) and a positive correlation between the concentration of IL-10 with the duration of DM (Spearman’s correlation coefficient 0.379, p < 0.039). Conclusions. Mean levels of IL-6 were significantly elevated in men with type 2 diabetes aged 50 years and older. Mean IL-10 levels were significantly elevated in men with type 2 diabetes regardless of the age of the patients. A significant positive correlation was found between the indicators of IL-6 and IL-10 in the examined patients with type 2 diabetes regardless of age also in patients with type 1 diabetes mellitus.

scholarly journals Hand functions in type 1 and type 2 diabetes mellitus

2017 ◽  
Vol 145 (11-12) ◽  
pp. 584-588
Author(s):  
Pinar Akpinar ◽  
Afitap Icagasioglu ◽  
Esra Selimoglu ◽  
Banu Mesci
Keyword(s):  
Diabetes Mellitus ◽  
Grip Strength ◽  
Control Group ◽  
Hand Functions ◽  
Type 2 Dm ◽  
Significant Difference ◽  
Hand Disability ◽  
Type 1 Dm

Introduction/Objective. Hand functions have an enormous impact on activities of daily living in patients with diabetes mellitus (DM), such as self-care, administering insulin injections, and preparing and eating meals. The aim of the study was to evaluate hand functions and grip strength in patients with type 1 and type 2 DM. Methods. This was an observational case-control study investigating the hand functions and grip strength in patients with type 1 and type 2 DM. The study comprised 41 patients with type 1 DM aged 25?50 years sex- and age-matched, 40 non-diabetic controls, and 91 patients with type 2 DM aged 40?65 years sex- and age-matched 60 non-diabetic controls. Patients with documented history of diabetic sensorimotor neuropathy and adhesive capsulitis were excluded. The Duruoz Hand Index was used to assess the functional hand disability. Grip strength was tested with a calibrated Jamar dynamometer. Results. The Duruoz Hand Index scores in patients with type 2 DM were significantly higher than in persons in the control group (p < 0.01), but there was no significant difference between the type 1 DM and the control group (p > 0.05). Grip strength values of patients with type 1 DM were significantly lower compared to those in the control group (p < 0.05), whereas there was no significant difference between patients with type 2 DM and their control group. There was a negatively significant correlation between grip strength and the Duruoz Hand Index scores in patients with both type 1 and type 2 DM (p < 0.05). Conclusion. Patients with type 1 DM and type 2 DM have different degrees of hand disability as compared to healthy control groups.

Sign in / Sign up

Export Citation Format

Share Document