Insulin response was assessed in two cross-over experiments using an oral glucose tolerance test OGTT; experiment 1 and a hyperglycemic HG clamp experiment 2. Main outcomes were the percentage change of BPA session measures relative to those of the control session. Results Serum bioactive BPA after experimental exposure was at levels detected in human biomonitoring studies. In the HG clamp study, focusing on the later-phase insulin response to a stable level of glucose, several measures of insulin and C-peptide appeared suppressed during the BPA session relative to the control session; the change in insulin maximum concentration Cmax was negatively correlated with HbA1c and the Cmax of bioactive serum BPA.
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Adipocyte ABCA1 deficiency impairs glucose tolerance. Decreased insulin sensitivity in peripheral tissues results in increased insulin secretion by the pancreas to compensate for this insulin resistance 30 Increased production of insulin may eventually lead to beta-cell failure and reduced insulin secretion 30 Our findings support the paradigm that reduced beta-cell function can result from an increase in insulin demand as a consequence of insulin resistance in tissues.
Collectively, our data suggest that intracellular cholesterol homeostasis in adipocytes is maintained by ABCA1 and is crucial for glucose tolerance, insulin sensitivity, and beta-cell function. Alterations in adipocyte cholesterol are associated with adipose dysfunction and obesity, and ABCA1 has been shown to mediate cholesterol efflux from adipose tissue 79 Adipose tissue dysfunction is an important risk factor for the development of glucose intolerance, insulin resistance, and type 2 diabetes 31928 ; this indicates a role for adipocyte cholesterol and ABCA1 in these conditions.
Previous studies showing that cholesterol may be crucial in adipocyte function were mainly carried out in the 3T3 adipocyte cell line or observations in obese mice 34 In our study, we directly investigated how adipocyte ABCA1 affects adipose lipid content and adipose function using a mouse model specifically lacking ABCA1 in adipocytes.
In this study, we demonstrated significantly increased intracellular cholesterol levels in the adipose tissue of adipocyte ABCA1-deficient mice. This increase in cholesterol content is likely a direct effect of reduced ABCA1-mediated cholesterol efflux from adipose tissue.
Increased intracellular cholesterol has a major impact on lipid metabolism because cholesterol regulates the expression of multiple genes involved in intracellular lipid homeostasis.
For example, increased intracellular cholesterol reduces the expression of hmgcoA reductase and the ldlr via SREBP2 to reduce cholesterol synthesis and uptake 16 In addition, the generation of oxysterols from intracellular cholesterol activates the LXR transcription factor, which increases the expression of cholesterol efflux genes including abca1 and abcg1 16 In this study, we observed decreased ldlr expression and an increase in abcg1 expression in ABCA1-deficient adipose tissue.
We believe that the absence of ABCA1 induces cholesterol accumulation and influences various compensatory mechanisms to regulate cholesterol balance in adipocytes. Increased ABCG1 to enhance cholesterol efflux and decreased LDLR to reduce cholesterol uptake suggest that compensatory mechanisms are conserved in the adipocyte to regulate cholesterol homeostasis.
It has been suggested that intracellular cholesterol influences TG stores in adipose tissue 3 It has been shown in vitro that increased ABCA1-mediated cholesterol efflux from adipocytes occurs following the stimulation of TG lipolysis 78. This suggests that adipocyte ABCA1 is crucial for proper adipose tissue function in response to dietary fat and cholesterol.
Our observations also indicate that loss of adipocyte ABCA1 and subsequent increase in intracellular cholesterol levels are sufficient to influence whole-body glucose tolerance. Increased body weight and adipocyte TG accumulation are associated with adipocyte dysfunction, which may lead to a number of metabolic disturbances including glucose intolerance, insulin resistance, and hepatosteatosis 181921 Metabolic disturbances are affected by adipose tissue through the release of NEFAs and adipokines in plasma 1219 Increased NEFA flux from adipose tissue to liver, muscle, and pancreas has been shown to reduce insulin sensitivity and secretion 19 Expression and release of adiponectin shows an inverse correlation with adipose mass 219 Decreased levels of adiponectin reduce insulin sensitivity and stimulate hepatic lipid accumulation 219 In plasma, we observed a decrease in HMW adiponectin, which is the metabolically most active form of adiponectin.
This decrease in plasma HMW adiponectin may therefore contribute to the insulin resistance and glucose intolerance, as well as the hepatic lipid accumulation, we observed in our mouse model. GLUT-4 deficiency in adipose tissue has been shown to impair whole-body glucose tolerance and muscle insulin resistance, but this effect is independent of circulating NEFAs, TGs, or leptin This suggests that other unknown mechanisms associated with GLUT-4 may play a role in modulating insulin resistance.
In an effort to identify other mechanisms by which adipocyte ABCA1 deficiency affects whole-body glucose homoeostasis, we investigated the expression of genes and proteins involved in glucose metabolism in the liver. We did not observe altered levels of pAKT in the liver.Molecular Weight: Synonyms: Periplogenin-D-glucosid ; Periplogenin-D-glucosid [German] 1H NMR prediction.
Birth weight: There is a relationship between birth weight and developing diabetes, and it's the opposite of what one might intuitively think.
The lower the birth weight, the higher the risk of type 2 diabetes. What Is Prediction Of The Molecular Weight Of Glucose ABSTRACT The effect of molecular weight and time on the rate of diffusion was resolved using the agar-water gel test A petri dish containing three wells was used in the the agar-water gel set up.
One drop of each of the three substances, potassium permanganate (KMnO4), potassium dichromate (K2Cr2O7) and methylene blue, was placed to each.
In feature-based methods, biologically meaningful properties of a protein such as frequency of residues, molecular weight, secondary structure, extinction coefficients and other physicochemical properties are extracted from the primary sequence.
Research Article Ursolic acid improves lipid and glucose metabolism in high-fat-fed C57BL/6J mice by activating peroxisome proliferator-activated receptor alpha and hepatic autophagy. Glucose was able to diffuse through the MWCO pore because it was small enough, having a molecular weight of g/mol.
Albumin was unable to pass through because it was far too large, having a molecular weight in the range of s of g/mol.