scholarly journals High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

2021 ◽  
Vol 22 (13) ◽  
pp. 6660
Author(s):  
Agnese Filippello ◽  
Stefania Di Mauro ◽  
Alessandra Scamporrino ◽  
Roberta Malaguarnera ◽  
Sebastiano Alfio Torrisi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Stem Cell ◽  
Cell Differentiation ◽  
High Glucose ◽  
Intestinal Stem Cell ◽  
Stem Cell Markers ◽  
Chronic Hyperglycemia ◽  
Intestinal Organoids ◽  
L Cell

Intestinal organoids are used to analyze the differentiation of enteroendocrine cells (EECs) and to manipulate their density for treating type 2 diabetes. EEC differentiation is a continuous process tightly regulated in the gut by a complex regulatory network. However, the effect of chronic hyperglycemia, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This study aimed to investigate the effect of glucotoxicity on EEC differentiation in small intestinal organoid platforms. Mouse intestinal organoids were cultured in the presence/absence of high glucose concentrations (35 mM) for 48 h to mimic glucotoxicity. Chronic hyperglycemia impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it also reduced the expression of Gcg and GLP-1 positive cell number. In addition, the expression of intestinal stem cell markers was reduced in organoids exposed to high glucose concentrations. Our data indicate that glucotoxicity impairs L-cell differentiation, which could be associated with decreased intestinal stem cell proliferative capacity. This study provides the identification of new targets involved in new molecular signaling mechanisms impaired by glucotoxicity that could be a useful tool for the treatment of type 2 diabetes.

scholarly journals Dysregulation of a novel miR-23b/27b-p53 axis impairs muscle stem cell differentiation of humans with type 2 diabetes

2017 ◽  
Vol 6 (7) ◽  
pp. 770-779 ◽  
Author(s):  
Tora I. Henriksen ◽  
Peter K. Davidsen ◽  
Maria Pedersen ◽  
Heidi S. Schultz ◽  
Ninna S. Hansen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Muscle Stem Cell

Wogonin Alleviates Hyperglycemia Through Increased Glucose Entry into Cells Via AKT/GLUT4 Pathway

2019 ◽  
Vol 25 (23) ◽  
pp. 2602-2606 ◽  
Author(s):  
Shahzad Khan ◽  
Mohammad A. Kamal
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Modern World ◽  
Major Health Problem ◽  
Major Health ◽  
Chronic Hyperglycemia ◽  
Main Factor

: Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.

scholarly journals The frequency of Tim-3 on circulating Tfh cells was increased in type 2 diabetes mellitus patients

2020 ◽  
Vol 18 ◽  
pp. 205873922098280
Author(s):  
Shuai Guo ◽  
Xujie Yu ◽  
Limei Wang ◽  
Jing Jing ◽  
Yuanyuan Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Tfh Cells ◽  
Fasting Plasma ◽  
Healthy Donors

Type 2 diabetes mellitus (T2DM) is a chronic, low-grade inflammation disease. T follicular helper (Tfh) cells and T cell immunoglobulin and mucin domain 3 (Tim-3) are implicated in many immune diseases. This study aims to explore whether Tim-3 expression on Tfh cells is associated with T2DM progression. White blood cells (WBCs) were harvested from 30 patients with T2DM and 20 healthy donors. The abundance of circulating Tfh cells (cTfh) and the frequency of Tim-3 were analyzed by flow cytometry. Levels of fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C), and fasting plasma C-peptide were measured. Body mass index (BMI) and diabetes duration were also recorded. Patients with T2DM had higher numbers of cTfh cells. In addition, cTfh cells showed a negative correlation with HbA1C and diabetes duration, a positive correlation with fasting plasma C-peptide. The frequency of Tim-3 on cTfh cells was higher among T2DM patients compared with healthy donors. The in vitro experiment showed that high glucose levels increased the abundance cTfh cells but had no effect on Tim-3 expression. Our results suggest that cTfh cells and associated Tim-3 frequency may contribute to the progression of T2DM, and high glucose levels may influence cTfh cells directly.

scholarly journals Unraveling the Control of Cell Cycle Periods during Intestinal Stem Cell Differentiation

2018 ◽  
Vol 115 (11) ◽  
pp. 2250-2258 ◽  
Author(s):  
Richard Ballweg ◽  
Suengwon Lee ◽  
Xiaonan Han ◽  
Philip K. Maini ◽  
Helen Byrne ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Intestinal Stem Cell

scholarly journals Type 2 Diabetes Mellitus. From the start – combination therapy

2018 ◽  
Vol 21 (5) ◽  
pp. 386-394 ◽  
Author(s):  
Francesco Indovina ◽  
Pierpaolo Falcetta ◽  
Stefano Del Prato
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Diabetes Diagnosis ◽  
Good Glycemic Control ◽  
Chronic Hyperglycemia ◽  
Increased Risk ◽  
History Of ◽  
First Time ◽  
Early Combination Therapy

Modern treatment of T2DM requires a shift in paradigm with appropriate intensification of therapy from the very first time of diabetes diagnosis. This is supported by data showing how even a moderate delay in achieving good glycemic control can translate into a later increased risk of developing diabetic complications. The recognition of the complexity of the pathogenesis of T2DM leads to the appreciation of the importance of attacking the disease from different angles, i.e. simultaneous tackling of multiple mechanisms contributing to hyperglycemia. From the turn of century a growing number of new anti-hyperglycemic agents have been made available. As compared to the older ones, these new medicines have a more targeted mechanism of action as they act at the level of the specific pathophysiologic disturbances accounting the development and progression of hyperglycemia. Because of that drugs can be use in combination taking advantage of their complementary mechanisms of action and synergistic. If introduced earlier in the natural history of the disease combination therapy may contribute avoiding undesirable exposure to even mild chronic hyperglycemia and provide early benefits. With respect to that in this review we will discuss advantages, disadvantages and still unanswered questions related to the use of early combination therapy in type 2 diabetes.

scholarly journals CD36 regulates β cell differentiation and influences type 2 diabetic sepsis

2021 ◽  
Author(s):  
Huogen Liu ◽  
Ling Gu ◽  
Yundi Shi ◽  
Hailin Shu ◽  
Fengming Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Cell Clone ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Β Cell ◽  
Type 2 Diabetic

Abstract Background This study aimed to investigate the diagnostic function of CD36 in type 2 diabetic (T2DM) sepsis complications (T2DSC) and its effect on β-cell differentiation. Methods First, Age - and sex-matched T2DM patients, T2DSC patients and healthy people (50 cases each) were included. Quantitative polymerase chain reaction was used to measure CD36, FOXO1, PDX1, MAFA, insulin, SOX9, Neurog3 and NANOG expression in blood samples. Second, cultured human β-cell line EndoC-βH1 and the interference and overexpression of CD36. Cell clone, apoptosis, inflammatory cytokine, oxidative stress and β-cell differentiation related proteins were also analysed. Third, examined the role of CD36 in high glucose, LPS-induced β-cell. Results CD36 mRNA, and endocrine progenitor β-cell biomarkers SOX9, Neurog3 and NANOG were significantly increased in T2DM than control group, whereas the β-cell maturation biomarkers FOXO1, PDX1, MAFA and insulin were significantly decreased. Compared with the T2DM group, CD36 and FOXO1 were significantly increased in T2DSC, but PDX1, insulin, MAFA, SOX9, Neurog3 and NANOG were significantly decreased. The receiver operating characteristic curve revealed that CD36 was useful for distinguishing T2MD and T2DSC from the control group. Furthermore, CD36 overexpression increased β-cell apoptosis and the secretion of IL-1β, IL-8 TNF-α, malondialdehyde and reactive oxygen species. CD36 induced cell defferentiation. Lastly, CD36 knockdown could inhibit the high glucose and LPS-induced cell apoptosis, inflammatory, oxidative stress and cell defferentiation. Conclusion Significant increase in CD36 can be used as a biomarker for T2MD and T2DSC. CD36 promotes T2MD or T2DSC development by inducing β-cell inflammatory and oxidative stress and defferentiation.

scholarly journals Hemoglobin Levels in Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 3 (1) ◽  
pp. 24-29
Author(s):  
Wahyu Anita Khoirin ◽  
Rodhi Hartono
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Medical Records ◽  
Renal Interstitium ◽  
Chronic Hyperglycemia ◽  
Hypoxic Environment ◽  
Age Category

Type 2 diabetes mellitus with chronic hyperglycemia can cause a hypoxic environment in the renal interstitium and can cause kidney disorders (diabetic nephropathy), this can lead to decreased kidney function and the production of erythropoietin produced by peritubular fibroblasts is disrupted, and hemoglobin is not formed optimally and occurs anemia. Thei purposei ofi thisi studyi wasi toi determinei hemoglobini levelsi in patients withi typei 2i diabetesi mellitusi in RSUD. K.R.M.T Wongsonegoro Semarang. This is a descriptive quantitative study, the data comes from the medical records of patients with typei 2i diabetesi mellitusi withi complicationsi ofi diabetici nephropathyi at RSUD K.R.M.T Wongsonegoro Semarang as many as 40 samples with non-probability samplingi itechnique. The results showed that there were 20 men who had decreased hemoglobin levels and 1 person who had normal hemoglobin levels. Meanwhile, in women, 17 people had decreased hemoglobin levels and 2 people had normal hemoglobin levels. Based on the age category, the most were the early elderly as many as 15 people and the least in the late teens and early adults each as many as 2 people. Meanwhile, based on the average level of anemia, more experienced moderate levels of anemia. Hemoglobin levels in patients with type. 2i. diabetesi. mellitusi. withi. complicationsi. ofi. diabetici. nephropathyi. at RSUD K.R.M.T Wongsonegoro Semarang were 40 samples, on average they had low hemoglobin levels.

scholarly journals Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes-Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Muhammad Sohail Khan ◽  
Muhammad Ikram ◽  
Tae Ju Park ◽  
Myeong Ok Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Acid Oxidation ◽  
Chronic Hyperglycemia ◽  
Underlying Mechanisms

The pathology and neurodegeneration in type 2 diabetes- (T2D-) mediated Alzheimer’s disease (AD) have been reported in several studies. Despite the lack of information regarding the basic underlying mechanisms involved in the development of T2D-mediated AD, some common features of the two conditions have been reported, such as brain atrophy, reduced cerebral glucose metabolism, and insulin resistance. T2D phenotypes such as glucose dyshomeostasis, insulin resistance, impaired insulin signaling, and systemic inflammatory cytokines have been shown to be involved in the progression of AD pathology by increasing amyloid-beta accumulation, tau hyperphosphorylation, and overall neuroinflammation. Similarly, oxidative stress, mitochondrial dysfunction, and the generation of advanced glycation end products (AGEs) and their receptor (RAGE) as a result of chronic hyperglycemia may serve as critical links between diabetes and AD. The natural dietary polyflavonoid anthocyanin enhances insulin sensitivity, attenuates insulin resistance at the level of the target tissues, inhibits free fatty acid oxidation, and abrogates the release of peripheral inflammatory cytokines in obese (prediabetic) individuals, which are responsible for insulin resistance, systemic hyperglycemia, systemic inflammation, brain metabolism dyshomeostasis, amyloid-beta accumulation, and neuroinflammatory responses. In this review, we have shown that obesity may induce T2D-mediated AD and assessed the recent therapeutic advances, especially the use of anthocyanin, against T2D-mediated AD pathology. Taken together, the findings of current studies may help elucidate a new approach for the prevention and treatment of T2D-mediated AD by using the polyflavonoid anthocyanin.

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