ABSTRACT
Obesity,a risk factor for type 2 diabetes mellitus (T2DM),hypertension,cardiovascular diseases and cancers et al,has become a major global health problem.Multiple fundamental studies have revealed that obese subject is under a status of low-grade,chronic inflammation,which contributes to the development of insulin resistance and T2DM.Thus,anti-inflammatory treatment of T2DM has been greatly developed.Yet,so far,the effectiveness of anti-inflammatory therapy is controversial,which implies that the researchers need to re-examine the association between inflammation,insulin resistance and T2DM.In this reviews,we will focus on the relationships between obese-associated inflammation and insulin resistance and the trigger mechanism of this inflammation.
ABSTRACT
To develop standard in vitro chondrosarcoma models, we synthesized three hydrogels (i. e., PDMAAm, PNaAMPS and PMETAC) and investigated the influence of Young's modulus, swelling ratio and electric charges on the behavior of chondrosarcoma cells seeded on the hydrogels, including morphology, adhesion and aggregation. Results showed that the morphology of chondrosarcoma cells at 6h was dependent on the charges of hydrogels; cells present spindle-shaped and round-shaped morphology on negative charged and neutral hydrogel, respectively, while no cells spreaded on positive charged hydrogel. Chondrosarcoma cells formed aggregates on neutral PDMAAm after further culture. The hydrogels can be synthesized easily and has the characteristics of ease at use with defined components, which holds great potential for developing standard chondrosarcoma models in vitro.
Subject(s)
Humans , Bone Neoplasms , Pathology , Cell Line, Tumor , Cell Proliferation , Chondrosarcoma , Pathology , Hydrogels , Chemistry , Pharmacology , Methacrylates , Pharmacology , Nylons , Pharmacology , Static ElectricityABSTRACT
Insulin increases microvascular perfusion and substrate exchange surface area in muscle, which is pivotal for hormone action and substrate exchange, by activating insulin signaling cascade in the endothelial cells to produce nitric oxide. This action of insulin is closely coupled with its metabolic action and type 2 diabetes is associated with both metabolic and microvascular insulin resistance. Muscle microvascular perfusion/volume can be assessed by 1-methylxanthine metabolism, contrast-enhanced ultrasound and positron emission tomography. In addition to insulin, several factors have been shown to recruit muscle microvasculature, including exercise or muscle contraction, mixed meals, glucagon-like peptide 1 and angiotensin II type 1 receptor (AT1R) blocker. On the other hand, factors that cause metabolic insulin resistance, such as inflammatory cytokines, free fatty acids, and selective activation of the AT1R, are capable of causing microvascular insulin resistance. Therapies targeting microvascular insulin resistance may help prevent or control diabetes and decrease the associated cardiovascular morbidity and mortality.
Subject(s)
Cytokines , Endothelial Cells , Endothelium , Fatty Acids, Nonesterified , Glucagon-Like Peptide 1 , Hand , Insulin , Insulin Resistance , Meals , Microcirculation , Microvessels , Muscle Contraction , Muscles , Nitric Oxide , Perfusion , Positron-Emission Tomography , Receptor, Angiotensin, Type 1 , Vasoconstriction , Vasodilation , XanthinesABSTRACT
Under normal physiology, insulin exerts vasodilatory and pro-survival actions via the phosphati dylinositol 3-kinase (PI3-kinase) pathway and vasoconstrictive and mitogenic actions via the mitogen-activated protein kinase (MAPK) pathway in the vasculature. In the insulin resistant states, insulin signals through the PI3-kinase pathway are blunted but its signals through the MAPK cascade remain intact. This imbalance predisposes insulin resistant patients to hypertension and atherosclerosis. The renin-angiotensin system (RAS) is expressed both systemically and locally in the cardiovascular system. Insulin resistance up-regulates the local RAS which contributes to the pathogenesis of hypertension, heart failure, and atherosclerosis. Angiotensin Ⅱ impairs insulin signaling, induces inflammation via the NF-κB pathway, reduces nitric oxide availability and facilitates vasoconstriction,leading to insulin resistance and endothelial dysfunction. Thus the RAS, insulin resistance and inflammation perpetuate each other and coordinately contribute to endothelial dysfunction, vascular injury and atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and mortality and the incidence of new onset Type 2 diabetes.
ABSTRACT
Sister chromatid exchange (SCE) frequencies were investigated in 35 diabetics and 24 controls. The spontaneous and MMC-induced SCE frequencies in diabetics were obviously higher than those in controls. There was a significant positive correlation between the spontaneous and MMC-induced SCE frequencies in either diabetics or controls. No correlation was found between the spontaneous SCE frequencies and HbA1 . High concentrations of glucose or regular insulin in the culture medium could not increase SCE frequencies of the controls. No significant difference was found between the untreated patients and patients treated with tolbutamide. The increased SCE frequency in diabetics may account for higher incidence of fetal stillbirth, abortion and malformations in diabetic pregnancies.