scholarly journals Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Elena V Tchetina ◽  
Galina A Markova ◽  
Eugeniya P Sharapova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
The Body ◽  
Whole Body ◽  
Insulin Resistant ◽  
Resistant State ◽  
Insulin Resistant State

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.

scholarly journals The Aqueous Extract of Gynura divaricata (L.) DC. Improves Glucose and Lipid Metabolism and Ameliorates Type 2 Diabetes Mellitus

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Jinnan Li ◽  
Jinlei Feng ◽  
Hong Wei ◽  
Qunying Liu ◽  
Ting Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Water Extract ◽  
The Body ◽  
Peripheral Tissues ◽  
Insulin Resistant ◽  
Glucose And Lipid Metabolism

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia and dyslipidemia caused by impaired insulin secretion and resistance of the peripheral tissues. A major pathogenesis of T2DM is obesity-associated insulin resistance. Gynura divaricata (L.) DC. (GD) is a natural plant and has been reported to have numerous health-promoting effects on both animals and humans. In this study, we aimed to elucidate the regulatory mechanism of GD improving glucose and lipid metabolism in an obesity animal model induced by high-fat and high-sugar diet in combination with low dose of streptozocin and an insulin-resistant HepG2 cell model induced by dexamethasone. The study showed that the water extract of GD (GD extract A) could significantly reduce fasting serum glucose, reverse dyslipidemia and pancreatic damage, and regulate the body weight of mice. We also found that GD extract A had low toxicity in vivo and in vitro. Furthermore, GD extract A may increase glucose consumption in insulin-resistant HepG2 cells, markedly inhibit NF-κB activation, and decrease the impairment in signaling molecules of insulin pathway, such as IRS-1, AKT, and GLUT1. Overall, the results indicate that GD extract A is a promising candidate for the prevention and treatment of T2DM.

scholarly journals Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling

2017 ◽  
Vol 313 (3) ◽  
pp. R290-R297 ◽  
Author(s):  
K. M. Fanning ◽  
B. Pfisterer ◽  
A. T. Davis ◽  
T. D. Presley ◽  
I. M. Williams ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Radiation Exposure ◽  
Microvascular Density ◽  
Whole Body ◽  
Ecm Remodeling

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques ( Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.

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.

scholarly journals Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ping Wang ◽  
Huili Liu ◽  
Li Chen ◽  
Yingli Duan ◽  
Qunli Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Whole Body ◽  
Glucokinase Activator ◽  
Liver And Pancreas

Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS), and glucagon (FG) were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.

scholarly journals CORRELATION BETWEEN APOPROTEIN B/APOPROTEIN A-I RATIO WITH HOMA IR VALUE (HOMEOSTATIC MODEL ASSESMENT INSULIN RESISTANCE) IN TYPE 2 DIABETES MELLITUS

2019 ◽  
Vol 3 (2) ◽  
pp. 78
Author(s):  
Muhammad Rafli Afandi ◽  
Ferdy Royland Marpaung
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Pearson Correlation ◽  
The Body ◽  
Apoprotein B ◽  
Pearson Correlation Test ◽  
Homeostatic Model

Background: Diabetes mellitus (DM) is the seventh leading cause of death in the world (the occuring rate has reached 400 million people). Type2 DM is caused by the body cells’ inability to respond normally to insulin (insulin resistance). Homeostatic Model Assessment-Insuline Resistance (HOMA-IR) is a calculation method which function is to measure the body insulin resistance. Diabetes mellitus can cause lipid metabolism disorders (dyslipidemia) resulting in an increased level of LDL cholesterol and decreased HDL cholesterol. The apoprotein B/apoprotein A-I ratio is the result of comparisons of apoprotein B (LDL protein constituent) and apoprotein A-I (HDL protein constituent). The apo B/apo A-I ratio represents a balance between LDL cholesterol (atherogenic) and HDL (anti-atherogenic). It is astrong signifier in predicting heart disease. Purpose: This study aim to determine the correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus. Methods: Observasional, consecutive, 100 people with type 2 diabetes mellitus who is examined in apoprotein B, apoprotein A-I test that calculating the ratio in which ratio are calculated, as well as HOMA-IR in Parahita Clinical Laboratory Surabaya. This study uses Pearson correlation test method with SPSS 22.0 for Windows program. Results: The result of Pearson correlation test between apoprotein B/apoprotein A-I ratio with HOMA-IR in 100 samples is a strong and significant correlation value  (r=0,610, p<0,05).Conclusion: There is a strong correlation between the apoprotein B/apoprotein A-I ratio with HOMA-IR in patients with type 2 diabetes mellitus.

scholarly journals Serum resistin and adiponectin relationships with glucometabolic control in patients with type 2 diabetes mellitus

2018 ◽  
Vol 146 (5-6) ◽  
pp. 285-290
Author(s):  
Regaeiy Al ◽  
Syed Habib ◽  
Dokhi Al ◽  
Anwar Jammah ◽  
Mohammad Subhan
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
The Body ◽  
Poor Glycemic Control ◽  
Serum Adiponectin ◽  
Control Subjects

Introduction/Objective. Adiponectin and resistin are important adipokines that play an important role in the regulation of blood sugar, beta-oxidation in muscles, and insulin resistance. This study aimed to assess and compare the relationships of resistin and adiponectin concentrations with glucometabolic control in patients with type 2 diabetes mellitus (T2DM). Methods. A total of 191 subjects were studied. The final selection included 107 patients with T2DM (67 males and 40 females) and 84 healthy control subjects (45 males and 39 females). Fasting venous blood samples were analyzed for glucose (FBG), glycosylated hemoglobin (HbA1c), insulin, lipids, adiponectin and resistin levels. Body composition was evaluated in all subjects by the body mass index (BMI) and waist?hip ratio (WHR). Results. BMI, WHR, FBG, HbA1c, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, and triglycerides were significantly higher in individuals with T2DM compared to healthy volunteers. Serum resistin levels were significantly higher (p = 0.0259) and serum adiponectin levels were significantly lower (p = 0.0001) in T2DM patients than in control subjects. Adiponectin levels were significantly lower (p = 0.0411) in diabetes patients with poor glycemic control, compared to those with good glycemic control, while the difference was non-significant for resistin (p = 0.8899). Serum adiponectin levels were discordant with HbA1c (r = -0.274, p = 0.004). Linear-by-linear association showed significant trend of better glycemic control at increasing quartiles of adiponectin levels (p = 0.042), while the trend was not significant for resistin levels (p = 0.904). Multiple regression analysis revealed FBG, insulin, HOMA-IR, and HbA1c as significant predictors of adiponectin. Conclusions. T2DM patients have significantly higher resistin and lower adiponectin levels compared to healthy controls. Adiponectin levels were significantly lower in patients with poor glycemic control.

scholarly journals DEMONSTRATION OF PRECISE RELATIONSHIPS AND LINKS BETWEEN TYPE 2 DIABETES MELLITUS, INSULIN RESISTANCE AND PARKINSON’S DISEASE

2020 ◽  
Vol 7 (12) ◽  
pp. 259-270
Author(s):  
Habib ur Rehman ◽  
Kaleemullah ◽  
Abdul Malik Tareen
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Type 2 Diabetes Mellitus ◽  
The Body ◽  
Diabetic Patients ◽  
The Brain

Diabetes is a metabolic disorder that intessssrferes with the body's ability to consume food and convert it into energy. The most common mode of diabetes in type 2 diabetes mellitus (T2DM) is that the body cannot effectively use insulin produced by the pancreas. This is called insulin resistance. Parkinson's Disease (PD) is a chronic neurodegenerative motor defect whose properties work is hindrance with locomotion. This is due to the loss of neurons in the substantia nigra area under the brain that produces dopamine, a chemical messenger that transmits signals that produce smooth, meaningful movement. Dopamine loss caused by neuronal damage and death causes impaired movement. Cells rely on glucose for energy, and insulin helps to convert glucose into energy. In both Parkinson's disease and type 2 diabetes, changes in the brain can result in signaling interruptions that affect normal functioning. Insulin resistance also reaches the brain and produces severe changes in the nerve cells, increasing the risk of Parkinson's disease and abnormally promoting high blood sugar leads to high-rise the inflammation, associated with the development of Parkinson's disease. Diabetes suffering peoples are more likely to have Parkinson's disease. Parkinson's disease is 32% higher in people with type 2 diabetes than in non-diabetic patients. Patients with type 2 diabetes along with its complication have a 49% higher risk of Parkinson’s disease, while those having only type 2 diabetes without complications have a 30% risk of parkinson’s disease. In particular, younger patients with diabetes (25 to 44 years of age) have an approximately fourfold increased risk of developing Parkinson's compared with adults of similar age without diabetes. Researchers has estimated the high risk of developing PD based on longitudinal data methodology for people with type 2 diabetes. Initial studies have reported more than 400 genes linked in both conditions. The potential link between type 2 diabetes and Parkinson's disease has been the topic of medical dialogue and scientific research for years. Recently, animal and in vitro studies have shown that the pathophysiology and clinical symptoms of Parkinson's disease are concerned more with insulin dysregulation and changes in insulin action.

scholarly journals Prognostic factors for the carbohydrate metabolism normalization in patients with type 2 diabetes mellitus and obesity using liraglutide 3.0 mg per day

2021 ◽  
Vol 93 (10) ◽  
pp. 1203-1208
Author(s):  
Igor A. Sklyanik ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Carbohydrate Metabolism ◽  
Fasting Blood Glucose ◽  
The Body ◽  
Hypoglycemic Effect ◽  
Antihyperglycemic Therapy

Background. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are innovative drugs that effectively reduce glycemic levels and overweight in patients with type 2 diabetes mellitus (T2DM). However, the criteria for predicting the hypoglycemic effect of this group of drugs have not been practically defined. Aim. To assess the factors contributing to the achievement the glycemia normalization in patients with diabetes mellitus and obesity by adding to antihyperglycemic therapy (AT) a drug from the GLP-1 RA group liraglutide 3.0 mg per day. Materials and methods. A single-center, prospective, non-randomized study was provided. The objects of the study were patients with T2DM and obesity (n=22). Liraglutide 3.0 mg per day was added to the current AT of patients. Initially, the parameters of carbohydrate metabolism, hormones of the incretin system on an empty stomach and during the mixed-meal test, insulin resistance using the euglycemic hyperinsulinemic clamp test, and body composition were studied. After 9 months of therapy, all studies were repeated and a search for possible predictors of the carbohydrate metabolism normalization was made. Results. The body mass index of patients decreased from 42.4 [37.7; 45.0] to 35.9 [33.0; 40.9] kg/m2. Fasting blood glucose and glycated hemoglobin levels decreased from 9.02 [7.40; 11.37] mmol/L and 7.85 [7.43; 8.65]% up to 5.90 [5.12; 6.18] mmol/L and 6.40 [5.90; 6.60]%, respectively. 14 (63.6%) patients reached normoglycemia. Insulin resistance according to the clamp test did not change over the study. Basal concentrations of oxyntomodulin, glycentin and the area under the GLP-1, oxyntomodulin, glycentin curve significantly decreased 9 months after liraglutide administration. The prognostic marker of the achievement of normoglycemia during therapy with liraglutide 3.0 mg/day is the level of endogenous GLP-15.5 pmol/L before the appointment of arGPP-1 therapy. Conclusion. The concentration of endogenous GLP-1 before the appointment of liraglutide therapy at a dose of 3.0 mg per day can be used for prediction the drug hypoglycemic effect and achieving normoglycemia possibility.

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