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Insulin

About: Insulin is a research topic. Over the lifetime, 124295 publications have been published within this topic receiving 5129734 citations. The topic is also known as: human insulin.


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Journal ArticleDOI
01 Jul 2010-Diabetes
TL;DR: These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity and indicates they metabolize lipid and may initiate adaptive immune responses.
Abstract: OBJECTIVE Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity. RESEARCH DESIGN AND METHODS Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c+CD206+ cells in “crown” aggregates and solitary CD11c−CD206+ cells at adipocyte junctions. In obese women, CD11c+ ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c+ ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1β, -6, -8, and -10; tumor necrosis factor-α; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c+ ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c− ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c+ ATMs, but not CD11c− ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes. CONCLUSIONS These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c+ ATMs indicates they metabolize lipid and may initiate adaptive immune responses.

532 citations

Journal ArticleDOI
TL;DR: Young adults with a very low birth weight have higher indexes of insulin resistance and glucose intolerance and higher blood pressure than those born at term and adjustment for the lower lean body mass in the very-low-birth-weight subjects did not attenuate these relationships.
Abstract: BACKGROUND The association between small size at birth and impaired glucose regulation later in life is well established in persons born at term. Preterm birth with very low birth weight (<1500 g) is also associated with insulin resistance in childhood. If insulin resistance persists into adulthood, preterm birth with very low birth weight also may be associated with an increased risk of disease in adulthood. We assessed glucose tolerance and insulin sensitivity and measured serum lipid levels and blood pressure in young adults with very low birth weight. METHODS We performed a standard 75-g oral glucose-tolerance test, measuring insulin and glucose concentrations at baseline and at 120 minutes in 163 young adults (age range, 18 to 27 years) with very low birth weight and in 169 subjects who had been born at term and were not small for gestational age. The two groups were similar with regard to age, sex, and birth hospital. We measured blood pressure and serum lipid levels, and in 150 very-low-birth-weight subjects and 136 subjects born at term, we also measured body composition by means of dual-energy x-ray absorptiometry. RESULTS As compared with the subjects born at term, the very-low-birth-weight subjects had a 6.7% increase in the 2-hour glucose concentration (95% confidence interval [CI], 0.8 to 12.9), a 16.7% increase in the fasting insulin concentration (95% CI, 4.6 to 30.2), a 40.0% increase in the 2-hour insulin concentration (95% CI, 17.5 to 66.8), an 18.9% increase in the insulin-resistance index determined by homeostatic model assessment (95% CI, 5.7 to 33.7), and an increase of 4.8 mm Hg in systolic blood pressure (95% CI, 2.1 to 7.4). Adjustment for the lower lean body mass in the very-low-birth-weight subjects did not attenuate these relationships. CONCLUSIONS Young adults with a very low birth weight have higher indexes of insulin resistance and glucose intolerance and higher blood pressure than those born at term.

532 citations

Journal ArticleDOI
TL;DR: It is shown that insulin regulates HIF-1 action through a PI3K/TOR-dependent pathway, resulting in increased VEGF expression in retinal epithelial cells.

531 citations

Journal ArticleDOI
01 Sep 2010-Obesity
TL;DR: This study focused on characterizing AcylCN profiles in human plasma from individuals with obesity and T2DM during fasting and insulin‐stimulated conditions, suggesting that more fatty acids can enter mitochondria.
Abstract: Dysregulation of fatty acid oxidation (FAO) is recognized as important in the pathophysiology of obesity and insulin resistance (IR). However, demonstrating FAO defects in vivo in humans has entailed complex and invasive methodologies. Recently, the identification of genetic blocks in FAO has been vastly simplified by using tandem mass spectrometry (MS/MS) of dried bloodspots to specify acylcarnitine (AcylCN) alterations characteristic for each disorder. This technology has recently been applied to examine FAO alterations in human and animal models of obesity and type 2 diabetes mellitus (T2DM). This study focused on characterizing AcylCN profiles in human plasma from individuals with obesity and T2DM during fasting and insulin-stimulated conditions. Following an overnight fast, plasma was obtained from lean (n = 12), obese nondiabetic (n = 14), and T2DM (n = 10) participants and analyzed for AcylCN using MS/MS. Plasma samples were also obtained at the end of a 4-h insulin-stimulated euglycemic clamp. In obesity and T2DM, long-chain AcylCNs were similarly significantly increased in the fasted state; free-CN levels were also elevated. Additionally, T2DM subjects of comparable BMI had increased short- and medium-chain AcylCNs, both saturated and hydroxy, as well as increased C(4)-dicarboxylcarnitine (C(4)DC-CN) that correlated with an index of poor glycemic control (HbA(1c); r = 0.74; P < 0.0001). Insulin infusion reduced all species of plasma AcylCN but this reduction was blunted in T2DM. Plasma long-chain AcylCN species are increased in obesity and T2DM, suggesting that more fatty acids can enter mitochondria. In T2DM, many shorter species accumulate, suggesting that they have a generalized complex oxidation defect.

531 citations

Journal ArticleDOI
TL;DR: It is concluded that insulin activates the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly through production of a ligand that activates LXRs or their heterodimerizing partner, the retinoid X receptor.
Abstract: Transcription of the gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP-1c protein activates transcription of the genes required for fatty acid synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the mechanism of insulin activation in freshly isolated rat hepatocytes. The data show that a complete insulin response (increase of 6- to 11-fold) requires two binding sites for liver X receptors (LXRs), which are nuclear receptors that are activated by oxygenated sterols. Disruption of these binding sites did not lower basal transcription but severely reduced the response to insulin. In contrast, disruption of the closely linked binding sites for SREBPs and nuclear factor Y lowered basal transcription drastically but still permitted a 4- to 7-fold increase in response to insulin. Arachidonic acid, an inhibitor of LXR activation, blocked the response to insulin. We conclude that insulin activates the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly through production of a ligand that activates LXRs or their heterodimerizing partner, the retinoid X receptor. Nuclear SREBPs and nuclear factor Y play permissive roles.

531 citations


Network Information
Related Topics (5)
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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20243
20232,520
20225,252
20213,164
20203,368
20193,376