A New Model of Primary Human Adipocytes Reveals Reduced Early Insulin Signalling in Type 2 Diabetes

2004 ◽  
Vol 36 (8) ◽  
pp. 531-537 ◽  
Author(s):  
P. Algenstaedt ◽  
N. Rosenblatt ◽  
I. Kolb ◽  
A. Krützelmann ◽  
B. Schwarzloh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signalling ◽  
Human Adipocytes ◽  
New Model

Inhibition of FOXO1 transcription factor in primary human adipocytes mimics the insulin-resistant state of type 2 diabetes

2018 ◽  
Vol 475 (10) ◽  
pp. 1807-1820 ◽  
Author(s):  
Meenu R. Rajan ◽  
Elin Nyman ◽  
Cecilia Brännmark ◽  
Charlotta S. Olofsson ◽  
Peter Strålfors
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Insulin Signalling ◽  
Regulation Of Transcription ◽  
Human Adipocytes ◽  
Insulin Resistant ◽  
Resistant State ◽  
Insulin Resistant State

Type 2 diabetes is characterized by insulin resistance in the expanding adipose tissue of obesity. The insulin resistance manifests in human adipocytes as system-wide impairment of insulin signalling. An exception is the regulation of transcription factor FOXO1 (forkhead box protein O1), which is phosphorylated downstream of mTORC2 (mammalian/mechanistic target of rapamycin in complex with raptor) and is therefore not exhibiting impaired response to insulin. However, the abundance, and activity, of FOXO1 is reduced by half in adipocytes from patients with diabetes. To elucidate the effect of reduced FOXO1 activity, we here transduced human adipocytes with a dominant-negative construct of FOXO1 (DN-FOXO1). Inhibition of FOXO1 reduced the abundance of insulin receptor, glucose transporter-4, ribosomal protein S6, mTOR and raptor. Functionally, inhibition of FOXO1 induced an insulin-resistant state network-wide, a state that qualitatively and quantitatively mimicked adipocytes from patients with type 2 diabetes. In contrast, and in accordance with these effects of DN-FOXO1, overexpression of wild-type FOXO1 appeared to augment insulin signalling. We combined experimental data with mathematical modelling to show that the impaired insulin signalling in FOXO1-inhibited cells to a large extent can be explained by reduced mTORC1 activity — a mechanism that defines much of the diabetic state in human adipocytes. Our findings demonstrate that FOXO1 is critical for maintaining normal insulin signalling of human adipocytes.

Comprehensive Review on Neuro-Degenerative Type 3DM

2021 ◽  
Vol 18 ◽  
Author(s):  
Chandani V. Chandarana ◽  
Salona Roy
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Diabetes Mellitus Type 1 ◽  
Current Data ◽  
The Body ◽  
Type I ◽  
Therapeutic Benefits

: Alzheimer disease (AD) is thought to be the metabolic illness raised by defective insulin signaling, insulin resistance, and low insulin levels in the brain, according to a growing body of research. The "Type 3 diabetes" has been postulated for AD because reduced insulin signalling has molecular and physiological consequences that are comparable to Type I and Type 2 diabetes mellitus (Type 1 DM and Type 2 DM, respectively). The similarities between type 2 diabetes and Alzheimer's disease suggest that these clinical trials might yield therapeutic benefits. However, it's important to note that lowering your risk of Alzheimer's dementia, whether you have diabetes or not, is still a multidimensional process involving factors like exercise, smoking, alcohol, food, and mental challenge. The current aim is to show the relationship between T3D and AD being based on both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are the result of an impaired insulin signaling. The brain's metabolism with its high lipid content and energy needs, places excess demands on mitochondria and appears more susceptible to oxidative damage than the rest of the body. Current data suggests that increased oxidative stress relates to amyloid-β (Aβ) pathology and onset of AD.

scholarly journals Type 2 Diabetes Mellitus and Alzheimer’s Disease: Role of Insulin Signalling and Therapeutic Implications

2018 ◽  
Vol 19 (11) ◽  
pp. 3306 ◽  
Author(s):  
Andrea Tumminia ◽  
Federica Vinciguerra ◽  
Miriam Parisi ◽  
Lucia Frittitta
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Cell Activation ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Neuronal Stem Cell

In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer’s disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.

Medical service demands of older patients in different age groups in a new model of free Telemedicine

2020 ◽  
Author(s):  
Yu Gong ◽  
Jianyuan Zhou
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Older Patients ◽  
Medical Service ◽  
Age Groups ◽  
New Model

Abstract Background Medical service for the older patients is a worldwide challenge for public health system. Telemedicine can provide convenient and effective medical service for older patients. But the existing telemedicine models rely upon a direct communication between a doctor and a patient via the Internet but the doctor would be unable to give the patient a direct physical examination, it may lead to diagnostic errors. A new model of telemedicine jointly performed by general practitioners in community health centers and specialists in a university teaching hospital has been established. It is supervised by the government health department and is free for older patients. However, medical service demands of older patients in different age groups applying the new telemedicine are not well characterized. This study is to analyze medical service demands of older patients in different age groups applying the new telemedicine. Methods 472 older patients (aged ≥ 60) were enrolled and were divided into the young older group (aged 60 to 74), the old older group (aged 75 to 89) and the very old group (aged ≥ 90) according to the age stratification for older people defined by World Health Organization. Proportion of the top 10 diseases of older patients of different age groups was analyzed. Results Coronary heart disease and type 2 diabetes mellitus were identified as the top two diseases in the older patients and the young older patients as well as the old older patients applying the new telemedicine. Conclusions The new telemedicine model can provide effective free medical services to older patients. Different medical service demands were identified in different age groups of older patients. Coronary heart disease and type 2 diabetes mellitus were the main diseases of the older patients and young older patients as well as the old older patients applying the new telemedicine. Results of this study will provide basis for the health administrative departments to formulate health policies for older patients. Familiar with the main diseases in different age groups of older patients may provide better medical services to older patients.

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 The Characterization of High-Fat Diet and Multiple Low-Dose Streptozotocin Induced Type 2 Diabetes Rat Model

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Ming Zhang ◽  
Xiao-Yan Lv ◽  
Jing Li ◽  
Zhi-Gang Xu ◽  
Li Chen
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
High Fat Diet ◽  
Low Dose ◽  
Tolerance Test ◽  
Male Rats ◽  
High Fat ◽  
New Model ◽  
Injection Group

Aim. Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high-fat diet combined with multiple low-dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine.Method. Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high-fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism.Result. The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin resistance, hyperglycemia, and blood lipid disorder. All these symptoms observed in the 30 mg/kg STZ twice injection group were recovered by the treatment of berberine.Conclusion. Together, these results indicated that high-fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening.

Review on Potential Vitamin D Mechanism with Type 2 Diabetes Mellitus Pathophysiology in Malaysia

2018 ◽  
Vol 6 (1) ◽  
pp. 01-11 ◽  
Author(s):  
Nurliyana Najwa bt Md Razip ◽  
Huzwah bt Khaza'ai
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Signalling ◽  
Relevant Literature ◽  
Resistance Mechanisms ◽  
Cross Sectional ◽  
Disease Study

Evidences on vitamin D deficiency suggest there is increasing risk of diabetes. To date, some cohort, observation, cross-sectional studies on populations and randomized controlled trials in vitamin D supplements highlighting the potential of vitamin D are essentially in modifying Type 2 Diabetes Mellitus (T2DM) pathophysiology. Relevant literature sought in a various databases focus on the discovery of vitamin D studies in Malaysia, particularly in dietary, health status and disease study. However, recent data in Malaysia, the scope of the literature focuses on the deficient vitamin D mediated insulin impairment. The development of literary findings encompasses on the etiology of diabetes which highly correlates with decreased mechanism of action of vitamin D. It is important to understand diabetes etiology before explaining more about insulin resistance mechanisms which is strongly correlated with the involvement of c-Jun N-terminal kinase (JNK) pathways in insulin signalling. Furthermore, the vitamin D works synergistically with calcium homeostasis which is believed to have interaction with insulin. The purpose of this article is to illustrate the potential of vitamin D in modulating T2DM pathophysiology. Existing evidence showing the biochemical function of vitamin D is strongly involved in the pathogenesis of T2DM which requires considerable attention.

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