scholarly journals In situ transplantation of adipose-derived stem cells via photoactivation improves glucose metabolism in obese mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luochen Zhu ◽  
Ziqian Feng ◽  
Xin Shu ◽  
Qian Gao ◽  
Jiaqi Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Epididymal Adipose Tissue ◽  
Adipose Derived Stem Cells ◽  
Combined Application

Abstract Background Accumulating evidence suggests that enhanced adipose tissue macrophages (ATMs) are associated with metabolic disorders in obesity and type 2 diabetes. However, therapeutic persistence and reduced homing stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Methods We demonstrate that the effect of a combined application of photoactivation and adipose-derived stem cells (ASCs) using transplantation into visceral epididymal adipose tissue (EAT) in obesity. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Results In diet-induced obesity, implantation of light-treated ASCs improved glucose tolerance and ameliorated systemic insulin resistance. Intriguingly, compared with non-light-treated ASCs, light-treated ASCs reduced monocyte infiltration and the levels of ATMs in EAT. Moreover, implantation of light-treated ASCs exerts more anti-inflammatory effects by suppressing M1 polarization and enhancing macrophage M2 polarization in EAT. Mass spectrometry revealed that light-treated human obese ASCs conditioned medium retained a more complete secretome with significant downregulation of pro-inflammatory cytokines and chemokines. Conclusions These data suggest that the combined application of photoactivation and ASCs using transplantation into dysfunctional adipose tissue contribute to selective suppression of inflammatory responses and protection from insulin resistance in obesity and type 2 diabetes.

scholarly journals GABA-stimulated adipose-derived stem cells suppress subcutaneous adipose inflammation in obesity

2019 ◽  
pp. 201822067 ◽  
Author(s):  
Injae Hwang ◽  
Kyuri Jo ◽  
Kyung Cheul Shin ◽  
Jong In Kim ◽  
Yul Ji ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Epididymal Adipose Tissue ◽  
Adipose Derived Stem Cells ◽  
Tissue Macrophage ◽  
Monocyte Migration ◽  
Fat Depot ◽  
Subcutaneous Adipose

Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABAB receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.

scholarly journals ID: 1080 Adipose-derived stem cells alleviate glucose tolerance in type 2 diabetic mouse

2017 ◽  
Vol 4 (S) ◽  
pp. 166
Author(s):  
Anh Nguyen Tu Bui ◽  
Cong Le Thanh Nguyen ◽  
Anh Thi Minh Nguyen ◽  
Nhat Chau Truong ◽  
Ngoc Kim Phan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Stem Cells ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Human Ascs ◽  
Type 2 Diabetic

Background: Type 2 diabetes (T2D) is the most common form of diabetes and accounts for 90-95% of all existing diabetic cases. The main etiologies of T2D include insulin resistance in target tissues, insufficient secretion of insulin and subsequent decline of pancreatic β-cell function. Recently, many studies have suggested that adipose – derived stem cells (ASCs) were potential to alleviate insulin resistance and hyperglycemia and promote the islets repair. In this study, ASCs were hypothesized that they could have ameliorative effects on type 2 diabetic mice.  Methods: Type 2 diabetic mice were induced by a combination of high-fat diet and injection of STZ 100 mg/kg and NA 120 mg/kg. Thereafter, two doses of 106 human ASCs were transplanted 2 week interval into each mouse via the tail vein. The mice were monitored health condition, rate of mortaity, body weight, consumption of food and water, blood glucose level, serum insulin level and histological structure of pancreatic islets.  Results: Our results indicated that the ASC-treated mice expressed improved condition in comparision with non-treated diabetic mice. The consumption of food and water as well as the blood glucose level decreased. Simultaneously, ASC transplantation improved the impaired glucose tolerance and insulin tolerance in T2D mice. Besides, the total cholesterol have significantly decreased.  Conclusion: it is suggested that human ASCs infusion is safe and effective for type 2 diabetes mellitus in mice regarding the improved glucose metabolism and insulin resistance.

scholarly journals Adipose Tissue-Specific Deletion of 12/15-Lipoxygenase Protects Mice from the Consequences of a High-Fat Diet

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Banumathi K. Cole ◽  
Margaret A. Morris ◽  
Wojciech J. Grzesik ◽  
Kendall A. Leone ◽  
Jerry L. Nadler
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Epididymal Adipose Tissue ◽  
Wild Type ◽  
High Fat ◽  
Specific Deletion

Type 2 diabetes is associated with obesity, insulin resistance, and inflammation in adipose tissue. 12/15-Lipoxygenase (12/15-LO) generates proinflammatory lipid mediators, which induce inflammation in adipose tissue. Therefore we investigated the role of 12/15-LO activity in mouse white adipose tissue in promoting obesity-induced local and systemic inflammatory consequences. We generated a mouse model for fat-specific deletion of 12/15-LO,aP2-Cre;12/15-LOloxP/loxP, which we call ad-12/15-LO mice, and placed wild-type controls and ad-12/15-LO mice on a high-fat diet for 16 weeks and examined obesity-induced inflammation and insulin resistance. High-fat diet-fed ad-12/15-LO exhibited improved fasting glucose levels and glucose metabolism, and epididymal adipose tissue from these mice exhibited reduced inflammation and macrophage infiltration compared to wild-type mice. Furthermore, fat-specific deletion of 12/15-LO led to decreased peripheral pancreatic islet inflammation with enlarged pancreatic islets when mice were fed the high-fat diet compared to wild-type mice. These results suggest an interesting crosstalk between 12/15-LO expression in adipose tissue and inflammation in pancreatic islets. Therefore, deletion of 12/15-LO in adipose tissue can offer local and systemic protection from obesity-induced consequences, and blocking 12/15-LO activity in adipose tissue may be a novel therapeutic target in the treatment of type 2 diabetes.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

Insulin resistance and beta cell function in aboriginals with type 2 diabetes in Atlantic Canada

2000 ◽  
Vol 50 ◽  
pp. 108 ◽  
Author(s):  
Meng H. Tan ◽  
Sethu Reddy ◽  
Jean Abram ◽  
Pantelis Andreou ◽  
Danita Volder
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Atlantic Canada

An electrochemically deposited collagen wound matrix combined with adipose-derived stem cells improves cutaneous wound healing in a mouse model of type 2 diabetes

2018 ◽  
Vol 33 (4) ◽  
pp. 553-565 ◽  
Author(s):  
Nicole Edwards ◽  
Denis Feliers ◽  
Qingwei Zhao ◽  
Randolph Stone ◽  
Robert Christy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Stem Cells ◽  
Mouse Model ◽  
Chronic Wounds ◽  
High Porosity ◽  
Adipose Derived Stem Cells ◽  
Clinical Issue ◽  
Wound Matrix ◽  
Electrochemically Deposited

Chronic wounds complicated by diabetes are a significant clinical issue, and their occurrence is expected to continue to rise due to an increased prevalence of diabetes mellitus, especially type 2 diabetes. Diabetic wounds frequently lead to nonhealing ulcers, and often eventually result in limb amputation due to the high risk of infection of the chronic wound. Here, we present a tissue-engineered treatment that combines a novel electrochemically deposited collagen wound matrix and human adipose-derived stem cells. The matrix fabrication process is optimized for voltage and time, and the final collagen biomaterial is thoroughly characterized. This collagen material possesses high tensile strength, high porosity, and excellent biocompatibility and cellular proliferation capabilities. Human adipose-derived stem cells were seeded onto the collagen wound matrix and this construct is investigated in a full thickness excisional wound in a mouse model of type 2 diabetes. This novel treatment is shown to stimulate excellent healing and tissue regeneration, resulting in increased granulation tissue formation, epidermal thickness, and overall higher quality tissue reformation. Both the collagen wound matrix alone and collagen wound matrix in combination with adipose derived stem cells appeared to be excellent treatments for diabetic skin wounds, and in the future can also be optimized to treat other injuries such as burns, blast injuries, surgical incisions, and other traumatic injuries.

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