G Boden

..As increased plasma levels account for up to 50% of insulin resistance in obese patients with T2DM, lowering of plasma FFAs could be a new and promising approach to the treatment of T2DM...

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..We conclude that hyperinsulinemia, whether or not associated with insulin resistance, shifts the MMP/TIMP balance toward reduction of extracellular matrix degradation and thus may promote the development of hepatic fibrosis...

..To determine tissue factor procoagulant activity (TF-PCA) in patients with type 1 diabetes and to examine effects of hyperglycemia and hyperglycemia plus hyperinsulinemia on TF-PCA...

..5%) and increasing G(Rd) (442 vs. 330%). We conclude that RGZ/FFB is a promising new therapy for type 2 diabetes that lowers plasma FFA more than RGZ alone and in contrast to RGZ does not cause water retention and weight gain...

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..Therefore, obesity, if associated with elevated fatty acid levels, may lead to hyperglycemia in prediabetic but not in normal individuals...

..The insulin- and FFA-induced hyperactivity of three proatherogenic MMPs in vascular tissues may promote degradation of extracellular matrix over time, leading to thinning of atherosclerotic capsules and acute vascular problems...

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..We conclude that this type of acute ER stress is likely to occur during normal daily nutrient intake...

..We conclude that SMS completely prevented HG/HI-induced TF activation in normal volunteers and may be of use to reduce the procoagulant state and acute vascular events in hyperinsulinemic insulin-resistant patients with type 2 diabetes...

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..To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people...

..It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress...

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..To examine fat biopsy samples from lean insulin-sensitive and obese insulin-resistant nondiabetic individuals for evidence of endoplasmic reticulum (ER) stress...

..Here, we have examined the effects of physiologically elevated levels of insulin and FFA on three MMPs and their inhibitors (tissue inhibitors of MMP [TIMPs]) in aortic tissue of male rats during euglycemic-hyperinsulinemic clamping...

..Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation...

..This results in reduction of tyrosine phosphorylation of the insulin receptor substrate-1 and inhibits activation of phosphoinositol-3 kinase, an enzyme that is essential for normal insulin-stimulated glucose uptake...

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..Lastly, normalizing plasma FFA levels is proposed as a new approach to reducing insulin resistance and the risk for type 2 diabetes mellitus, and atherosclerotic vascular disease...

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..Free fatty acids (FFAs) have emerged as a major link between obesity and insulin resistance/type 2 diabetes mellitus. A review of the interaction between FFAs and glucose metabolism is therefore timely and relevant...

..Thus, elevated plasma levels of FFAs are not only a major cause of insulin resistance in skeletal muscle and liver but may, in addition, play a role in the pathogenesis of coronary artery disease...

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..This situation will lead to an increase in blood glucose concentration and eventually to type 2 diabetes. CONCLUSION: FFA have been shown to have an important contributing role in the pathogenesis of insulin resistance in human obesity...

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..We conclude that PDE-3 plays a major role in the inhibitory action of insulin on lipolysis in fat and on glucose production in liver and, in addition, seems to be involved in insulin secretion in pancreatic beta cells...

..Whether acute FFA-induced insulin resistance in human skeletal muscle is caused by the activation of these specific PKC isoforms and the IKK-beta/IkappaB/NFkappaB pathway remains to be established...

..We conclude that at insulin and FFA levels in the postprandial range, women and men were susceptible to FFA-induced peripheral and hepatic insulin resistance...

..We concluded that the women with GDM had a major ss-cell defect that made it impossible for them to compensate for their increased level of insulin resistance, which occurred during late pregnancy...

..We conclude that in type 1 diabetes acute regulation of EGP by insulin is mainly via changes in GL while GNG changes little during the early hours of acute insulin excess or deficiency...

..In obesity, however, there is no need to spare carbohydrate and the FFA induced insulin resistance may result in type 2 diabetes and other cardiovascular risk factors...

..We conclude that TZDs have multiple actions and that many, but perhaps not all, can be accounted for by their action on adipose tissue...

..Platelet responsiveness to activation with ADP or SFLLRN appears not to be altered by hyperglycemia-hyperinsulinemia...

..The long-term effects of this diet, however, remain uncertain...

..Little is known about the acute effects of resistance exercise on insulin sensitivity in people with type 1 diabetes...

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..Extremely low carbohydrate/high protein diets are popular methods of weight loss. Compliance with these diets is poor and long-term effectiveness and the safety of these diets for patients with type 2 diabetes is not known...

..9.2 micromol x kg(-1). min(-1), P < 0.05). We conclude that insulin suppressed EGP by inhibiting GL more than GNG and that elevated plasma FFA levels attenuated the suppression of EGP by interfering with insulin suppression of GL...

..These results establish Cdk4 as an essential regulator of specific cell types...

..Our data are most compatible with binding of one insulin molecule per human placental insulin receptor...

..We conclude that FFA-induced release of resistin may contribute to the development of FFA-induced insulin resistance in rats...

..This new ghrelin-associated peptide behaves as a physiological opponent of ghrelin in rodent animals, but its pathophysiological role in humans remains unknown..

..We conclude that short-term treatment of rats with Pio prevented lipid-induced hepatic insulin resistance and that Pio mediated lowering of blood resistin and raising of adiponectin levels may have contributed to that effect...

..Normalizing plasma FFA levels is, therefore, proposed as a novel approach to reduce insulin resistance, the risk of Type 2 diabetes mellitus and atherosclerotic vascular disease...

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..These studies will hopefully provide much needed information relative to important details and mechanisms of FFA induced hepatic insulin resistance. ..

..We believe that these studies will provide important new information relative to the mechanism by which obesity and FFAs cause IR and ASVD in human subjects. ..

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..We hope that this project will help to better understand the mechanisms by which obesity contributes to the development of NIDDM. ..

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