Reduction of Postprandial Hyperglycemia in Patients with Type 2 Diabetes Reduces NF-κB Activation in PBMCs

Rudofsky, Gottfried; Reismann, Péter; Schiekofer, Stephan; Petrov, D; Eynatten, M. von; Humpert, Per M.; Isermann, Berend; Müller-Hoff, Christiane Charlotte; Thai, Thanh-Phuong; Lichtenstein, Samuel V.; Bärtsch, U.; Hamann, Andreas; Nawroth, PP; Bierhaus, Angelika

doi:10.1055/s-2004-825904

Cited by 57 publications

(36 citation statements)

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“…However, the effect of the postprandial state, particularly postprandial hyperglycaemia, on CVD is still a matter of debate [21,22]; studies show that postprandial hyperglycaemia is accompanied by an increase of both oxidative stress and inflammatory markers [11][12][13][14][15]. This evidence is supported by findings showing an increase in vivo, during postprandial hyperglycaemia, of both protein kinase C and nuclear factor kappa B, two factors which regulate the generation of oxidative stress and inflammation [23,24].…”

Section: Discussionmentioning

confidence: 97%

“…However, the possibility that postprandial hyperglycaemia increases oxidative stress and inflammation in healthy subjects has previously been reported [12,13]. Furthermore, evidence showing that modulation of postprandial hyperglycaemia by diet or an insulin analogue in type 2 diabetes [25][26][27], and by pramlintide [28] in type 1 diabetes, is accompanied by a significant decrease of oxidative stress, while nuclear factor kappa B activation is decreased when controlling postprandial hyperglycaemia by acarbose [24], convincingly suggests that the effect of S21403 on postprandial oxidative stress and inflammation is related to its ability to reduce postprandial hyperglycaemia.…”

Section: Discussionmentioning

confidence: 98%

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Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Assaloni

Ros

Quagliaro³

et al. 2005

Diabetologia

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Aim/hypothesis: Evidence suggests that postprandial hyperglycaemia may be a cardiovascular risk factor in diabetes. Oxidative stress and inflammation are involved in the pathogenesis of diabetic complications and previous studies have shown increased oxidative stress and inflammation in the postprandial phase in diabetic patients. The aim of the present study was to evaluate whether controlling postprandial hyperglycaemia with S21403 (mitiglinide) is accompanied by a reduced generation of oxidative stress and inflammation. Subjects and methods: Forty type 2 diabetic patients participated in the study. Two different breakfast-tests were performed in each patient, with placebo or S21403. Plasma nitrotyrosine, plasma malondialdehyde (MDA), oxidised LDL (oxLDL), plasma total radical-trapping antioxidant parameter (TRAP), IL-6, IL-18, TNF-α, plasma glucose and insulin were measured. Results: After the administration of S21403, 40 mg, a rapid stimulation of insulin secretion was observed, accompanied by a reduction of postprandial hyperglycaemia. With S21403, a significant decrease of either nitrotyrosine, MDA and oxLDL levels, and a preservation of plasma TRAP compared with placebo was found. Significant decreases of IL-6, IL-18 and TNF-α were also observed with S21403 compared with placebo. Conclusions/interpretation: This study shows that controlling postprandial hyperglycaemia with S21403 significantly improves the cluster of oxidative stress and inflammation markers that are increased in the postprandial state in diabetic patients.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Assaloni

Ros

Quagliaro³

et al. 2005

Diabetologia

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“…42 High dietary fructose consumption (60% wt/wt in chow) also induces a stress response in liver and other tissues in tandem with insulin resistance and lipid metabolic dysregulation. 43 Our results indicate that fructose ingestion, in the absence of insulin resistance, is also capable of inducing a stress response in liver by increasing NF-B activity.…”

Section: Discussionmentioning

confidence: 99%

Impairment of hepatic Stat-3 activation and reduction of PPARα activity in fructose-fed rats

et al. 2007

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Fructose makes up a significant proportion of energy intake in westernized diets; its increased consumption has paralleled the growing prevalence of obesity and metabolic syndrome over the past two decades. In the current study, we demonstrate that fructose administration (10% wt/vol) in the drinking water of rats reduces the trans-activating and trans-repressing activity of the hepatic peroxisome proliferator-activated receptor ␣ (PPAR␣). As a consequence, fructose decreases hepatic fatty oxidation and increases pro-inflammatory transcription factor nuclear factor B (NF-B) activity. These changes were not observed in glucose-administered rats (10% wt/ vol), although both carbohydrates produced similar changes in plasma adiponectin and in the hepatic expression of transcription factors and enzymes involved in fatty acid synthesis. Fructosefed, but not glucose-fed, rats were hyperleptinemic and exhibited increased tyrosine phosphorylation of the signal transducer and activator of transcription-3 (STAT-3) transcription factor, although they did not present a similar increase in the serine phosphorylation of nuclear STAT3. Thus, an impairment in the hepatic transduction of the leptin signal could be responsible for the observed alterations in PPAR␣ activity in fructose-fed rats. Because PPAR␣ activity is lower in human than in rodent liver, fructose ingestion in humans should cause even worse effects, which would partly explain the link between increased consumption of fructose and widening epidemics of obesity and metabolic syndrome. T he prevalence of metabolic syndrome and the risk for developing diabetes mellitus and cardiovascular disease is increasing worldwide. 1,2 Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the types of nutrients, with an increased consumption of fructose, largely attributable to the greater intake of beverages containing high levels of fructose. 3 Once absorbed, dietary fructose is mainly taken up by the liver, promoting triacylglycerol synthesis and very low-density lipoprotein (VLDL) production. However, increases in liver fatty acid synthesis alone is not sufficient to account for such elevated triacylglycerol production. 4 Thus, those mechanisms underlying liver lipid metabolic derangements caused by high-fructose diets are not completely understood.The rat offers an effective model of human fructose metabolism. 5 A high-fructose diet in rats induces metabolic derangements similar to those found in the metabolic syndrome. 6 Nevertheless, although experimental designs using 50% to 60% of fructose in pelleted diets induce hypertriglyceridemia and a pronounced state of insulin resistance, 6,7 diets incorporating 10% wt/vol of fructose in drinking water induce hypertriglyceridemia and fatty liver without modifying plasma glucose and insulin levels. 8,9 Because high-carbohydrate diets and chronic hyperin...

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“…Short-term studies also have demonstrated benefits on postprandial lipemia and inflammatory markers. 63,64 One diabetes prevention study involving the ␣-glucosidase inhibitor acarbose demonstrated an impressive 91% relative risk reduction in MI compared with the control group, although the validity of these findings is challenged by the extremely low number of MI events evaluated (12 versus 1) and 24% attrition of study treatment. 65 These agents should be considered in patients with mild hyperglycemia, particularly when other drug options are limited because of preexisting contraindications.…”

Section: Inzucchi and Mcguire Diabetes Drugs: Incretin-based Therapy mentioning

confidence: 99%

New Drugs for the Treatment of Diabetes

2008

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Abstract-This is the second of a 2-part series focusing on newer therapies for type 2 diabetes and their cardiovascular implications. In the first segment, we reviewed the thiazolidinediones, highlighting emerging data concerning their cardiovascular effects, both positive and negative. Here, we present a corresponding discussion of the newest antihyperglycemic category, modulators of the incretin system, which include the glucagon-like peptide-1 mimetics and the dipeptidyl peptidase-4 inhibitors. In addition, we briefly survey several novel drug classes in development, provide summary recommendations for glucose-lowering regimens in specific patient types, underscore the importance of nonglucose cardiovascular risk reduction strategies, and comment on present and future considerations for the regulatory review of diabetes drugs. (Circulation. 2008;117:574-584.)Key Words: coronary disease Ⅲ diabetes mellitus Ⅲ drugs Ⅲ heart failure Ⅲ incretins A novel category of antihyperglycemic therapy based on modulation of the incretin system has recently emerged. Incretins are gut-derived peptides secreted in response to meals, specifically the presence and absorption of nutrients in the intestinal lumen. 1 The major incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). GLP-1 is produced by the neuroendocrine L cells of the ileum and colon; GIP is elaborated by K cells of the duodenum and jejunum. Both are released rapidly after meal intake; their secretion appears to be under neural control. GLP-1 and GIP stimulate insulin output from pancreatic ␤ cells in a glucose-dependent fashion (enhancement of secretion linked to the presence of hyperglycemia). In addition, GLP-1, but not GIP, decreases pancreatic ␣-cell secretion of glucagon, a hormone that augments hepatic glucose production. GLP-1 also retards gastric emptying and likely has a direct suppressive effect on central appetite centers. The cardinal physiological role of the incretin system appears to be the attenuation of postprandial glucose excursions. Notably, patients with type 2 diabetes mellitus (T2DM) are partially deficient in GLP-1 secretion, 2 a finding that has encouraged the development of drugs that augment GLP-1 levels or activity. Recently, however, the question of whether such incretin dysregulation is responsible for or is a consequence of the hyperglycemia in diabetes has been raised. 3 The first incretin modulator class encompasses the GLP-1 analogues or mimetics, which are functional agonists of the GLP-1 receptor. The initial approved member of this class is the injectable exenatide. Incretins are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), which is widely expressed in many tissues, including kidney, liver, lung, and the small intestine. 4 As a result, the half-lives of GLP-1 and GIP are measured in minutes. Oral inhibitors of DPP-4, in essence, increase the plasma concentrations of the biologically active form of endogenously secreted incretins. The first DPP-4 inhibitor is sitaglipti...

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Reduction of Postprandial Hyperglycemia in Patients with Type 2 Diabetes Reduces NF-κB Activation in PBMCs

Abstract: Reduction of postprandial glucose peak levels by acarbose reduces postprandial mononuclear NF-kappaB activation.

Cited by 57 publications

References 24 publications

Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients

Impairment of hepatic Stat-3 activation and reduction of PPARα activity in fructose-fed rats

New Drugs for the Treatment of Diabetes

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