Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression.

Background: The intake of glucose or a high-fat, high-carbohydrate (HFHC) meal, but not orange juice, induces an increase in inflammation and oxidative stress in circulating mononuclear cells (MNCs) of normal-weight subjects.

Objective: We investigated the effect of orange juice on HFHC meal-induced inflammation and oxidative stress and the expression of plasma endotoxin and Toll-like receptors (TLRs).

Design: Three groups (10 subjects in each group) of normal, healthy subjects were asked to drink water or 300 kcal glucose or orange juice in combination with a 900-kcal HFHC meal.

Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3.

Objective: We have recently shown that a high-fat high-carbohydrate (HFHC) meal induces an increase in plasma concentrations of endotoxin (lipopolysaccharide [LPS]) and the expression of Toll-like receptor-4 (TLR-4) and suppresser of cytokine signaling-3 (SOCS3) in mononuclear cells (MNCs) in addition to oxidative stress and cellular inflammation. Saturated fat and carbohydrates, components of the HFHC meal, known to induce oxidative stress and inflammation, also induce an increase in LPS, TLR-4, and SOCS3.

Research Design And Methods: Fasting normal subjects were given 300-calorie drinks of either glucose, saturated fat as cream, orange juice, or only water to ingest.

Insulin as an anti-inflammatory and antiatherogenic modulator.

Data demonstrate the anti-inflammatory effects of insulin and proinflammatory effects of glucose. These data provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in hospitalized patients. Regimens that infuse fixed doses of insulin with high rates of glucose are usually associated with hyperglycemia, which may neutralize the beneficial effects of insulin.

Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome.

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH.

Acute modulation of toll-like receptors by insulin.

Objective: Low-dose insulin infusion has been shown to exert a prompt and powerful anti-inflammatory effect. Toll-like receptors (TLRs) are major determinants of the inflammatory response to viral and bacterial pathogens. We have now hypothesized that low-dose insulin infusion in obese type 2 diabetic patients suppresses TLR expression.

Evaluation of Antioxidant Potential of Kaempferia rotunda Linn.

The plant Kaempferia rotunda Linn. has been explored for its anti oxidant potential in the present study. The antioxidant property was assessed by lipid peroxidation markers such as malonaldehyde (MDA) and 4-hydroxyl-2-nonenal (4-HNE).

A novel view of metabolic syndrome.

The metabolic syndrome, as described by Reaven, is a combination of obesity, insulin resistance, hypertension, hypertriglyceridemia, low HDL cholesterol, and hyperinsulinemia. The syndrome was recognized as a very high pro-atherogenic risk causing coronary heart disease. More recently, other features like an elevated plasma PAI -1 and CRP have been added to the syndrome.

Absence of insulin-induced vasodilation of internal carotid artery in type 2 diabetes.

Background: Impaired cerebrovascular reserve could contribute to the increased risk of strokes in type 2 diabetes. We have shown a vasodilatory effect of insulin on the internal carotid artery in healthy subjects. As absence of this effect could be responsible for the impairment of cerebral blood flow reserve demonstrated in this population, we have now investigated the effect of insulin on the internal carotid artery of type 2 diabetics.

Use of insulin to improve glycemic control in diabetes mellitus.

Background: The restoration of normoglycemia ensures the control of diabetic symptoms and reduction in microangiopathic complications in type 1 and type 2 diabetes. However, there is no conclusive evidence that intensive glycemic control alone will prevent macrovascular disease, the commonest cause of morbidity and mortality in type 2 diabetes. As atherosclerosis is an inflammatory condition, it is relevant that the two common insulin resistant states of obesity and type 2 diabetes have significant inflammatory processes, which promote atherosclerosis.

Thiazolidinediones-improving endothelial function and potential long-term benefits on cardiovascular disease in subjects with type 2 diabetes.

Endothelial dysfunction, which leads to impaired vasodilation, is an early event in the development of atherosclerosis. A number of mechanisms involving, for example, cell adhesion molecules, chemokines, and cytokines, contribute to this inflammatory disease, and insulin resistance plays a cardinal role in accelerating these processes. Hyperglycemia and other metabolic abnormalities that are commonly associated with insulin resistance also contribute to impaired endothelial function.

Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin.

Objective: To evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.

Methods: In this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005.

Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese.

Background: Because obesity is associated with chronic oxidative and inflammatory stress, and high-fat, high-carbohydrate meals induce significant oxidative and inflammatory stress in normal subjects, we have now hypothesized that the intake of a high-fat, high-carbohydrate meal would result in a greater and more prolonged oxidative and inflammatory stress in the obese than in normal subjects.

Methods: Ten normal-weight and eight obese subjects were given a high-fat, high-carbohydrate meal after an overnight fast. Blood samples were collected at baseline and hourly following the meal for 3 h.

Effect of hyperglycemia and insulin in acute coronary syndromes.

Previously published data clearly demonstrate that hyperglycemia worsens morbidity and mortality in patients in intensive care, those with acute myocardial infarction and stroke, and those undergoing coronary artery bypass grafting. The control of hyperglycemia with insulin infusion improves clinical outcomes in these patients. In this article, we discuss data that demonstrate a proinflammatory effect of glucose and free fatty acids and an anti-inflammatory effect of insulin.

Anti-inflammatory effects of insulin.

Purpose Of Review: This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit.

Recent Findings: The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease.

Anti-inflammatory effects of insulin and the pro-inflammatory effects of glucose.

Previously published data demonstrate clearly that hyperglycemia worsens morbidity and mortality in patients in intensive care, those with acute myocardial infarction and stroke, and those undergoing coronary artery bypass grafts. The control of hyperglycemia with insulin infusion improves clinical outcomes in all classes of patients mentioned above. In this article we discuss data demonstrating an anti-inflammatory effect of insulin and a pro-inflammatory effect of glucose and free fatty acids and provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in the hospitalized patient.

Orange juice or fructose intake does not induce oxidative and inflammatory response.

Objective: We have previously shown that 300 kcal from glucose intake induces a significant increase in reactive oxygen species (ROS) generation and nuclear factor-kappaB (NF-kappaB) binding in the circulating mononuclear cells in healthy normal subjects. We hypothesized that the intake of 300 calories as orange juice or fructose, the other major carbohydrate in orange juice, would induce a significantly smaller response than that of glucose.

Research Design And Methods: Four groups (eight subjects each) of normal-weight subjects were given a 300-cal drink of glucose (75 g), fructose (75 g), or orange juice or water sweetened with saccharin (control group) to drink, and then blood samples were collected.

Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease.

Previously published data demonstrate clearly that hyperglycemia worsens morbidity and mortality in patients in intensive care, those with acute myocardial infarction and stroke, and those who undergo coronary artery bypass grafting. The control of hyperglycemia with insulin infusion improves clinical outcomes in all these classes of patients. In this report, the investigators discuss data demonstrating an anti-inflammatory effect of insulin and a proinflammatory effect of glucose and free fatty acids and provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in hospitalized patients.

Anti-inflammatory effects of insulin and pro-inflammatory effects of glucose: relevance to the management of acute myocardial infarction and other acute coronary syndromes.

Hyperglycemia worsens morbidity and mortality for patients in intensive care or with acute myocardial infarction, stroke, or coronary artery bypass grafts. The control of hyperglycemia with insulin improves clinical outcomes for patients with these conditions. This article reviews the anti-inflammatory effects of insulin and pro-inflammatory effects of glucose and free fatty acids, and provides a mechanistic justification for maintaining euglycemia with insulin infusions.

Glucose ingestion induces an increase in intranuclear nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy human subjects.

Because hyperglycemia is a major detrimental factor in the prognosis of acute cardiovascular conditions such as acute myocardial infarction (AMI) and stroke, and because an acute glucose challenge in healthy subjects has been shown to induce oxidative stress in mononuclear cells (MNCs), we have now investigated whether glucose induces inflammatory stress at the cellular and molecular level. Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs. Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs.

Insulin infusion in acute illness.

The discovery of the antiinflammatory effect of insulin and the proinflammatory effect of glucose has not only provided novel insight into the mechanisms underlying several disease states but has also provided a rationale for the treatment of hyperglycemia in several acute clinical conditions. Van den Berghe et al. previously showed the benefits of intensive glycemic control with insulin in patients admitted to intensive care units.