Site specific modification of the human plasma proteome by methylglyoxal.

Increasing evidence identifies dicarbonyl stress from reactive glucose metabolites, such as methylglyoxal (MG), as a major pathogenic link between hyperglycemia and complications of diabetes. MG covalently modifies arginine residues, yet the site specificity of this modification has not been thoroughly investigated. Sites of MG adduction in the plasma proteome were identified using LC-MS/MS analysis in vitro following incubation of plasma proteins with MG.

Enhanced cholesterol efflux to HDL through the ABCA1 transporter in hypertriglyceridemia of type 2 diabetes.

Objective: Our objective was to examine the role of hypertriglyceridemia on the capacity of HDL to facilitate ABCA-1 mediated cholesterol efflux in type 2 diabetes (T2DM).

Methods: HDL mediated cholesterol efflux through the ABCA-1 transporter was measured using BHK cell lines in samples of 71 participants with T2DM in the presence or absence of high triglyceride levels (TG). Additionally, HDL mediated efflux was measured in 13 diabetic and non-diabetic participants fasting and four hours after a high-fat test challenge.

The effects of a community-based, culturally tailored diabetes prevention intervention for high-risk adults of Mexican descent.

Purpose: This article reports the results of a community-based, culturally tailored diabetes prevention program for overweight Mexican American adults on weight loss, waist circumference, diet and physical activity self-efficacy, and diet behaviors.

Methods: The intervention used content from the Diabetes Prevention Program but culturally tailored the delivery methods into a community-based program for Spanish-speaking adults of Mexican descent. The design was a randomized controlled trial (N = 58) comparing the effects of a 5-month educational intervention with an attention control group.

Challenges and success of recruiting and retention for a culturally tailored diabetes prevention program for adults of Mexican descent.

Purpose: The purpose of this article is to describe methods used to recruit and retain high-risk, Spanish-speaking adults of Mexican origin in a randomized clinical trial that adapts Diabetes Prevention Program (DPP) content into a community-based, culturally tailored intervention.

Methods: Multiple passive and active recruitment strategies were analyzed for effectiveness in reaching the recruitment goal. Of 91 potential participants assessed for eligibility, 58 participated in the study, with 38 in the intervention and 20 in the attention control group.

Adjusting for Urinary Creatinine Overestimates Arsenic Concentrations in Diabetics.

BACKGROUND/AIMS: Arsenic (As) is linked to insulin resistance in animal studies, but the effect of low-level As exposure on the prevalence of diabetes in humans is uncertain. An optimal method to report inorganic As in humans has not been established. Measurements of As in spot urine are usually adjusted to creatinine (Cr).

Erlotinib-associated exacerbation of hypothyroidism with pericardial tamponade.

Objective: To report a case of erlotinib-associated exacerbation of hypothyroidism complicated by pericardial tamponade.

Methods: We describe the patient's clinical presentation, biochemical workup, and clinical course.

Results: Non-small cell lung cancer was diagnosed in a 54-year-old woman.

Physical Activity in the Prevention of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD) and mortality. The increase in CKD in recent decades has paralleled increases in obesity, diabetes, and the metabolic syndrome. Physical inactivity is a modifiable risk factor that may affect the development and course of CKD.

Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes.

Context: A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa.

Objective: We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D.

Methods: We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) nondiabetic controls.

Effect of glucose or fat challenge on aspirin resistance in diabetes.

Aspirin has lower antiplatelet activity in diabetic patients. Our aim is to study the roles of acute hyperglycemia and hyperlipidemia on aspirin function in diabetic subjects with and without cardiovascular disease. Using urine thromboxane (pg/mg creatinine) and VerifyNow (Aspirin Resistance Measures-ARU), we investigated diabetic subjects during a 2-hour glucose challenge (n = 49) or a 4-hour fat challenge (n = 11).

Clinical determinants of aspirin resistance in diabetes.

Recent studies indicate that not all diabetic subjects benefit from aspirin therapy. Our objective is to characterize diabetic subjects with aspirin resistance using urine thromboxane, and VerifyNow measures. Our results suggest that cardiovascular disease, microalbuminuria, poor diabetes control, and increased waist circumference help identify aspirin resistance in diabetes.

Exercise training prevents development of cardiac contractile dysfunction in hypertensive TG (mREN-2)27 rats.

Background: Angiotensin-II (Ang-II) contributes to cardiac remodeling and left ventricular dysfunction. In contrast, exercise may have beneficial effects on left ventricular structure and function.

Methods And Results: We investigated the effects of low-intensity exercise training (ET) on in vivo cardiac function in hypertensive TG (mREN-2)27 rats (Ren-2) which develop left ventricular hypertrophy and dysfunction.

Effect of renin inhibition and AT1R blockade on myocardial remodeling in the transgenic Ren2 rat.

Angiotensin II (Ang II) stimulation of the Ang type 1 receptor (AT(1)R) facilitates myocardial remodeling through NADPH oxidase-mediated generation of oxidative stress. Components of the renin-angiotensin system constitute an autocrine/paracrine unit in the myocardium, including renin, which is the rate-limiting step in the generation of Ang II. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo renin inhibition and/or AT(1)R blockade in a rodent model of chronically elevated tissue Ang II levels, the transgenic (mRen2)27 rat (Ren2).

Adrenal steroids and the metabolic syndrome.

The many similarities between the metabolic syndrome and Cushing's syndrome led to the hypothesis that excess glucocorticoids (GC) are part of the pathogenesis linking their features. We review recent work that confirms the initial similarities (obesity, glucose intolerance, hypertension, and hyperlipidemia) and extends them to associated features of both syndromes (osteopenia, hypogonadism, leukocytosis, depression, and muscle weakness). Recent studies report that these features also occur in subclinical Cushing's syndrome, hypercortisolemic depression, and the transgenic overexpression of 11beta-hydoxysteroid dehydrogenase type 1 (11beta-HSD1) in mouse models of excess GC in adipose tissue.

Methods in the evaluation of cardiovascular renin angiotensin aldosterone activation and oxidative stress.

Renin angiotensin aldosterone system (RAAS) activation plays an essential role in the development of cardiovascular disease (CVD). Multiple pathophysiologic processes are able to activate RAAS, among which hypertension, obesity, diabetes mellitus 2, and chronic kidney disease deserve special attention, because they are the main contributors to CVD. Adding to the well-known effects of RAAS overactivity on the vasculature and water and electrolyte balance, current evidence links abnormal activation of the RAAS to increased production of reactive oxygen species (ROS) and oxidative stress.

Skeletal muscle insulin resistance: role of inflammatory cytokines and reactive oxygen species.

The cardiometabolic syndrome (CMS), with its increased risk for cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and chronic kidney disease (CKD), has become a growing worldwide health problem. Insulin resistance is a key factor for the development of the CMS and is strongly related to obesity, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), CKD, and NAFLD. Insulin resistance in skeletal muscle is particularly important since it is normally responsible for more than 75% of all insulin-mediated glucose disposal.

Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase.

Reduced insulin sensitivity is a key factor in the pathogenesis of type 2 diabetes and hypertension. Skeletal muscle insulin resistance is particularly important for its major role in insulin-mediated glucose disposal. Angiotensin II (ANG II) is integral in regulating blood pressure and plays a role in the pathogenesis of hypertension.

Metabolic derangements in the insulin-resistant heart.

Myocardium is flexible when it comes to energy substrate utilization; it uses fatty acid, glucose, lactones, and ketones for its energy requirement. The myocardial energy substrate preference varies in a dynamic manner depending on myocardial perfusion, energy demand, substrate availability, and local/systemic hormonal changes. The authors discuss the metabolic perturbations seen in insulin-resistant myocardium and how they result in structural and other biochemical changes that ultimately result in left ventricular hypertrophy and diastolic and systolic dysfunction.

Introduction: organ involvement in the cardiometabolic syndrome.

The cardiometabolic syndrome is a construct associated with an increased risk of type 2 diabetes mellitus, cardiovascular disease (coronary artery disease, peripheral arterial disease, and stroke), chronic kidney disease, and the metabolic hepatopathy referred to as nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. Thus, the term cardiometabolic syndrome includes all of these metabolic, islet, cardiovascular, renal, and hepatic disorders and clustering clinical syndromes. This overview of the cardiometabolic syndrome is designed to review the clinical complications and the end-organ cellular and extracellular matrix remodeling events that occur with the cardiometabolic syndrome.

Skeletal muscle insulin resistance is fundamental to the cardiometabolic syndrome.

The cardiometabolic syndrome is associated with insulin resistance and a dysregulation of glucose and lipid metabolism that occurs in multiple tissues. Of these, skeletal muscle is the most abundant insulin-sensitive tissue, handling > 40% of the postprandial glucose uptake, while consuming 20% of the body's energy. The inability to efficiently take up and store fuel, and to transition from fat to glucose as the primary source of fuel during times of plenty (increased insulin), has been termed metabolic inflexibility.

NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat.

Reduced insulin sensitivity is characteristic of various pathological conditions such as type 2 diabetes mellitus and hypertension. Angiotensin II, acting through its angiotensin type 1 receptor, inhibits the actions of insulin in the vasculature which may lead to deleterious effects such as vascular inflammation, remodeling, endothelial dysfunction, and insulin resistance. In contrast, insulin normally exerts vasodilatory, antiinflammatory, and prosurvival actions.

Exercise and diet induced weight loss improves measures of oxidative stress and insulin sensitivity in adults with characteristics of the metabolic syndrome.

Obesity and insulin resistance (IR) increase the risk for coronary heart disease; however, much of this risk is not attributable to traditional risk factors. We sought to determine whether weight loss associated with supervised aerobic exercise beneficially alters biomarkers of oxidative stress and whether these alterations are associated with improvements in measures of insulin resistance. Twenty-five sedentary and overweight to obese [body mass index (BMI) = 33.

Albumin activation of NAD(P)H oxidase activity is mediated via Rac1 in proximal tubule cells.

Background: Rac1 is a Rho-family small GTP-ase, when activated is pivotal in NAD(P)H oxidase (NOX) activation and generation of reactive oxygen species (ROS). Evidence links Rac1 activation to receptor-mediated albumin endocytosis in the proximal tubule cell (PTC). Thus in states of albumin overload, Rac1 activation could lead to NOX activation and ROS formation in the PTC.

Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia.

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.

Inactivity induces increases in abdominal fat.

Previously, inducing inactivity for 53 h after 21 days of voluntary running resulted in a 25 and 48% increase in epididymal and omental fat pad weights, respectively, while rats continued to eat more than a group that never had access to a running wheel (J Physiol 565: 911-925, 2005). We wanted to test the hypothesis that inactivity, independent of excessive caloric intake, could induce an increase in fat pad mass. Twenty-one-day-old rats were given access to voluntary running wheels for 42-43 days so that they were running approximately 9 km/day in the last week of running, after which wheels were locked for 5, 53, or 173 h (WL5, WL53, WL173) before the rats were killed.