Influence of glycaemic control on platelet bound CD40–CD40L system, P‐selectin and soluble CD40 ligand in Type 2 diabetes

Neubauer, H.; Setiadi, Patricia; Günesdogan, Bülent; Pinto, Antonio; Börgel, Jan; Mügge, Andreas

doi:10.1111/j.1464-5491.2010.02957.x

Cited by 34 publications

(23 citation statements)

References 30 publications

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“…Other researchers reported similar findings in a subsequent study in Europeans with T2D. 28 Interestingly, this latter publication also reported a significant decrease in platelet TNFR5 signalling following sustained reduction in haemoglobin A1C, indicating that the process may be reversible. A positive correlation between glycaemic control and sCD40L level has also recently been reported in patients with type 1 diabetes.…”

Section: Discussionsupporting

confidence: 66%

Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation

Bagnati

Ogunkolade

et al. 2016

Cell Death Dis

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Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal glucose homoeostasis is associated with, and exacerbated by, obesity and the concomitant-elevated free fatty acid concentrations typically found in these patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in insulin-producing β-cell mass through activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT)-1. There are however a large number of molecules potentially able to modulate NF-κB and STAT1 activity, and the mechanism(s) by which glucolipotoxicity initially induces NF-κB and STAT1 activation is currently poorly defined. Using high-density microarray analysis of the β-cell transcritptome, we have identified those genes and proteins most sensitive to glucose and fatty acid environment. Our data show that of those potentially able to activate STAT1 or NF-κB pathways, tumour necrosis factor receptor (TNFR)-5 is the most highly upregulated by glucolipotoxicity. Importantly, our data also show that the physiological ligand for TNFR5, CD40L, elicits NF-κB activity in β-cells, whereas selective knockdown of TNFR5 ameliorates glucolipotoxic induction of STAT1 expression and NF-κB activity. This data indicate for the first time that TNFR5 signalling has a major role in triggering glucolipotoxic islet cell death.

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Section: Discussionsupporting

confidence: 66%

Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation

Bagnati

Ogunkolade

et al. 2016

Cell Death Dis

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“…This has previously been observed in adults with T2D (9,10), in whom improved glycemic control correlated with a decline in measured platelet activation markers, suggesting that platelet hyperactivity can be reversed with improved metabolic control (9,10). The size of the current study did not allow for a comparison of subjects prescribed insulin with those who were not.…”

Section: Discussionmentioning

confidence: 61%

Markers of Platelet Activation Are Increased in Adolescents With Type 2 Diabetes

et al. 2014

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OBJECTIVEIn adults with diabetes, in vivo platelet activation is a marker for atherosclerosis and cardiovascular disease (CVD). This pilot study investigated whether adolescents with diabetes had evidence of increased in vivo platelet activation. RESEARCH DESIGN AND METHODSIn vivo platelet activation was compared in four groups of age-matched adolescents: type 1 diabetes (T1D, n = 15), type 2 diabetes (T2D; n = 15), control subjects with normal BMI (n = 14), and overweight/obese control subjects (n = 13). Platelet surface activation markers and plasma levels of soluble activation markers were measured and compared among groups. RESULTSIncreased expression of all activation markers was observed in T2D compared with either control group (P < 0.05); levels of soluble markers were also higher in T2D than in T1D (P < 0.05). There were no differences in marker expression between the nondiabetic control groups. CONCLUSIONSPlatelet activation in adolescents with T2D may be a marker for the risk of CVD development in early adulthood.Cardiovascular disease (CVD) is the primary cause of morbidity and mortality among adults with type 1 (T1D) and type 2 diabetes (T2D). Adults with diabetes have hyperactive platelets that are involved in the initiation and progression of atherosclerosis and in acute arterial thrombosis (1,2). The relationship among diabetes, platelet hyperactivity, and CVD is well established in adults (1,2). The same connection has not been made in adolescents with diabetes, despite observations that some of these adolescents, particularly those with T2D, have risk factors for accelerated progression of atherosclerosis and onset of CVD in early adulthood (3,4).The purpose of this pilot study was to determine whether we could identify in vivo platelet activation in adolescents with T1D or T2D compared with age-and BMI-matched nondiabetic control subjects by examining the expression of surfaceexpressed and soluble platelet activation markers. RESEARCH DESIGN AND METHODS Study ParticipantsAdolescents, ages 12-18 years, with T1D (n = 15), T2D (n = 15), and nondiabetic control subjects (n = 27: 14 with a normal BMI; 13 overweight or obese [OB]) were

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“…In the studies, where the acute coronary patients were enrolled, sCD40L was found as a marker of inflammatory thrombotic activity and found related with further increased cardiovascular events [21, 22]. Recently, CD40/CD40L pathway activation and a subsequent proinflamatory milieu were reported in diseases such as obesity [24, 25], diabetes mellitus [26] and hypertension [27]. Whether migraine patients constitute a low- or high-risk group for cardiovascular disease is obscure, but high-sCD40L levels in migraine patients in our study support the presence of a vascular damage in migraine.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period

Güldiken

Demir

et al. 2011

J Headache Pain

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The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients (p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels.

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Influence of glycaemic control on platelet bound CD40–CD40L system, P‐selectin and soluble CD40 ligand in Type 2 diabetes

Cited by 34 publications

References 30 publications

Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation

Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation

Markers of Platelet Activation Are Increased in Adolescents With Type 2 Diabetes

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period

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