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.

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.

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

scholarly journals Selenoprotein P as a significant regulator of pancreatic β cell function

2019 ◽  
Author(s):  
Yoshiro Saito
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Insulin Signalling ◽  
Selenoprotein P ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Β Cell Function

Abstract Selenoprotein P (SeP; encoded by SELENOP) is selenium (Se)-rich plasma protein that is mainly produced in the liver. SeP functions as a Se-transport protein to deliver Se from the liver to other tissues, such as the brain and testis. The protein plays a pivotal role in Se metabolism and antioxidative defense, and it has been identified as a ‘hepatokine’ that causes insulin resistance in type 2 diabetes. SeP levels are increased in type 2 diabetes patients, and excess SeP impairs insulin signalling, promoting insulin resistance. Furthermore, increased levels of SeP disturb the functioning of pancreatic β cells and inhibit insulin secretion. This review focuses on the biological function of SeP and the molecular mechanisms associated with the adverse effects of excess SeP on pancreatic β cells’ function, particularly with respect to redox reactions. Interactions between the liver and pancreas are also discussed.

scholarly journals Feed-forward signaling of TNF-α and NF-κB via IKK-β pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice

2009 ◽  
Vol 296 (6) ◽  
pp. H1850-H1858 ◽  
Author(s):  
Jiyeon Yang ◽  
Yoonjung Park ◽  
Hanrui Zhang ◽  
Xiangbin Xu ◽  
Glen A. Laine ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
Sodium Nitroprusside ◽  
Protein Modification ◽  
Nuclear Factor Κb ◽  
Diabetic Mice ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We hypothesized that the interaction between tumor necrosis factor-α (TNF-α)/nuclear factor-κB (NF-κB) via the activation of IKK-β may amplify one another, resulting in the evolution of vascular disease and insulin resistance associated with diabetes. To test this hypothesis, endothelium-dependent (ACh) and -independent (sodium nitroprusside) vasodilation of isolated, pressurized coronary arterioles from mLepr db (heterozygote, normal), Lepr db (homozygote, diabetic), and Lepr db mice null for TNF-α ( dbTNF−/ dbTNF−) were examined. Although the dilation of vessels to sodium nitroprusside was not different between Lepr db and mLepr db mice, the dilation to ACh was reduced in Lepr db mice. The NF-κB antagonist MG-132 or the IKK-β inhibitor sodium salicylate (NaSal) partially restored nitric oxide-mediated endothelium-dependent coronary arteriolar dilation in Lepr db mice, but the responses in mLepr db mice were unaffected. The protein expression of IKK-α and IKK-β were higher in Lepr db than in mLepr db mice; the expression of IKK-β, but not the expression of IKK-α, was attenuated by MG-132, the antioxidant apocynin, or the genetic deletion of TNF-α in diabetic mice. Lepr db mice showed an increased insulin resistance, but NaSal improved insulin sensitivity. The protein expression of TNF-α and NF-κB and the protein modification of phosphorylated (p)-IKK-β and p-JNK were greater in Lepr db mice, but NaSal attenuated TNF-α, NF-κB, p-IKK-β, and p-JNK in Lepr db mice. The ratio of p-insulin receptor substrate (IRS)-1 at Ser307 to IRS-1 was elevated in Lepr db compared with mLepr db mice; both NaSal and the JNK inhibitor SP-600125 reduced the p-IRS-1-to-IRS-1 ratio in Lepr db mice. MG-132 or the neutralization of TNF-α reduced superoxide production in Lepr db mice. In conclusion, our results indicate that the interaction between NF-κB and TNF-α signaling induces the activation of IKK-β and amplifies oxidative stress, leading to endothelial dysfunction in type 2 diabetes.

scholarly journals Effective Response to DPP-4 Inhibitors in Patients of COVID – 19 Triggered Uncontrolled Type 2 DM – A Case Report

2021 ◽  
pp. 34-38
Author(s):  
Akshay Dahiwele ◽  
Shailesh Patil ◽  
Sarju Zilate ◽  
Harsh Salankar ◽  
Sonali Rode
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Sugar ◽  
Blood Sugar Level ◽  
Glargine Insulin ◽  
Effective Response ◽  
Type 2 Dm ◽  
To Come

Introduction: A bidirectional relationship exist between the COVID -19 diagnosed & recovered patient and Type 2 Diabetes Mellitus. As per the various article available in public domain it has been proved that entry of COVID – 19 virus can lead to a series of pathological changes into a patient’s body which may lead to the development of insulin resistance and damage to the pancreas. The patient in our case was a COVID – 19 survivor which was diagnosed with type 2 DM during the treatment. The patient was started with the Glargine insulin when she was undergoing her treatment in the hospital for COVID – 19 Symptoms. Her fasting and postprandial blood sugar level was controlled with the insulin. After her discharged she was started with the Metformin 500 mg twice a day but her blood sugar was not controlled with the Metformin monotherapy, so we started with the triple drug combination Metformin + Glimepiride + Pioglitazone. After 1 month of follow-up, it was seen that the blood sugar level was not controlled, so the Pioglitazone was replaced with the DPP-4 inhibitor drug Vildagliptin and again the patient was asked to come for follow-up after 15 days, it was seen in this follow-up that the patients’ blood sugar was dramatically controlled. Conclusion: COVID – 19 triggered Type 2 DM is the result of cytokine storm develop during the disease. Metformin and DPP – 4 inhibitors reduce the insulin resistance in type 2 diabetes patients and helps to achieve the euglycemic goal of the patient.

scholarly journals A Novel TGR5 Activator WB403 Promotes GLP-1 Secretion and Preserves Pancreatic β-Cells in Type 2 Diabetic Mice

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0134051 ◽  
Author(s):  
Chunbing Zheng ◽  
Wenbo Zhou ◽  
Tongtong Wang ◽  
Panpan You ◽  
Yongliang Zhao ◽  
...  
Keyword(s):  
Diabetic Mice ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Type 2 Diabetic

scholarly journals Regenerative Medicine for Diabetes Mellitus

2009 ◽  
Vol 18 (5-6) ◽  
pp. 491-496 ◽  
Author(s):  
Naoya Kobayashi ◽  
Takeshi Yuasa ◽  
Teru Okitsu
Keyword(s):  
Regenerative Medicine ◽  
The Body ◽  
Definitive Treatment ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Living Body

In diabetes, a loss of pancreatic β-cells causes insulin dependency. When insulin dependency is caused by type 1 diabetes or pancreatic diabetes, for example, pancreatic β-cells need to be regenerated for definitive treatment. The methods for generating pancreatic β-cells include a method of creating pancreatic β-cells in vitro and implanting them into the body and a method of regenerating pancreatic β-cells in the body via gene introduction or the administration of differential proliferation factors to the body. Moreover, the number of pancreatic β-cells is also low in type 2 diabetes, caused by the compounding factors of insulin secretory failure and insulin resistance; therefore, if pancreatic β-cells can be regenerated in a living body, then a further amelioration of the pathology can be expected. The development of pancreatic β-cell-targeting regenerative medicine can lead to the next generation of diabetes treatment.

scholarly journals A study of the effects of large dose of parenteral vitamin D (D3) on insulin resistance in type 2 DM patients

2017 ◽  
Vol 5 (6) ◽  
pp. 2338
Author(s):  
Vinu Jamwal ◽  
Wani Zahid Hussain ◽  
Abhinav Gupta ◽  
Anil K. Gupta
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Insulin Sensitivity ◽  
Vitamin D3 ◽  
Favourable Effect ◽  
P Value ◽  
Low Grade ◽  
Β Cells ◽  
Pancreatic Β Cells

Background: Over the past decade, vitamin D is more known as a hormone because of its extra - skeletal outcomes in various disease conditions, including diabetes. Most cells, including the pancreatic β-cells, contain the vitamin D receptor and they also have the capability to produce the biologically active 1,25-dihydroxyvitamin D [1,25(OH)2D3] which allows intracrine and paracrine functions. In vitro studies have shown that the active vitamin D metabolite 1,25(OH)2D stimulated insulin release by the pancreatic β-cells. Vitamin D is known to have immune modulatory and anti-inflammatory effects and reduces peripheral insulin resistance by altering low-grade chronic inflammation. This study was done to assess whether supplementation of vitamin D in type 2 diabetes mellitus (T2DM) patients with Vitamin D deficiency has any favourable effect on insulin resistance.Methods: It was a short term interventional study conducted at ASCOMS hospital Jammu including a total of 50 vitamin D deficient [25(OH) D <50 nmol/l] T2DM patients with an in-adequate glycemic control (HbA1c > 7.0%). All the 50 study participants completed the study and there were no changes either in anti-hyperglycemic drugs (including insulin) or antihypertensive drugs being used. After supplementation with a single high dose (600000 IU) of parenteral vitamin D3 changes in HOMA-IR (Homeostasis model assessment insulin resistance) were seen on follow up at 3 months.Results: Vitamin D3 supplementation improved insulin sensitivity, HOMA-IR decreased from 4.05±1.42 to 3.93±1.28 (p =0.011). It decreased equally in males (3.85±1.43 to 3.76±1.30) (p value=0.023) and females (4.24±1.42 to 4.10±1.27) (p value=0.021). HOMA-IR showed negative association with Vitamin D levels both at baseline and after 3 months of follow up.Conclusions: This improvement in insulin sensitivity is evidenced in our study by decrease in fasting insulin levels (FIL) and improvement in fasting blood sugars (FBS). It is due to both direct and indirect effects of Vitamin D3 on both insulin sensitivity and secretion.

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