Maziyar Saberi

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Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. We discuss how(More)
Chronic low-grade inflammation, particularly in adipose tissue, is an important modulator of obesity-induced insulin resistance. The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages. We performed bone marrow transplantation (BMT) of Tlr4lps-del or control C57Bl/10J donor cells into irradiated wild-type C57Bl6 recipient(More)
Chromogranin A (CHGA/Chga), a proprotein, widely distributed in endocrine and neuroendocrine tissues (not expressed in muscle, liver, and adipose tissues), generates at least four bioactive peptides. One of those peptides, pancreastatin (PST), has been reported to interfere with insulin action. We generated a Chga knock-out (KO) mouse by the targeted(More)
Increases in adiposity trigger metabolic and inflammatory changes that interfere with insulin action in peripheral tissues, culminating in beta cell failure and overt diabetes. We found that the cAMP Response Element Binding protein (CREB) is activated in adipose cells under obese conditions, where it promotes insulin resistance by triggering expression of(More)
The transcription factor TORC2 [transducer of regulated cAMP-responsive element-binding protein (CREB) activity 2] is a major regulator of hepatic gluconeogenesis and is increased in hyperglycemic rodent models. Because chronic hyperglycemia and increased hepatic glucose production, via increased gluconeogenesis, is a key feature of type 2 diabetes, an(More)
Although peroxisome proliferator-activated receptor gamma (PPARgamma) agonists such as thiazolidinediones (TZDs) are widely used to treat type 2 diabetes, how its activation in individual tissues contributes to TZD's therapeutic action remains controversial. As TZDs are known to have receptor-independent effects, we sought to establish gain-of-function(More)
In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal(More)
Gastrointestinal bypass surgeries that result in rerouting and subsequent exclusion of nutrients from the duodenum appear to rapidly alleviate hyperglycemia and hyperinsulinemia independent of weight loss. While the mechanism(s) responsible for normalization of glucose homeostasis remains to be fully elucidated, this rapid normalization coupled with the(More)
Recent findings denote an important contribution of macrophage inflammatory pathways in causing obesity-related insulin resistance. Inducible nitric oxide synthase (iNOS) is activated in proinflammatory macrophages and modestly elevated in insulin-responsive tissues. Although the benefits of systemic iNOS inhibition in insulin-resistant models have been(More)
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