Effect of Dipyridamole on Blood Glucose and Liver Cyclic Amp Levels and Platelet Count During Endotoxaemia in Mice

Al-Jibouri, Layla M.; Najim, Rafid A.

doi:10.1111/j.1440-1681.1988.tb01110.x

Cited by 2 publications

(1 citation statement)

References 12 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several clinically used drugs inhibit ENT1 as a secondary mode of action, including rosuvastatin40 and dipyridamole 41. Interestingly, rosuvastatin increases HbA1c in individuals with and without diabetes,42 and dipyridamole increases glycaemia in mice 43. Taken together, these data suggest that therapeutic alterations in purine salvage may produce a clinically significant alteration in HGP via modulation of adenosine receptors.…”

Section: Discussionmentioning

confidence: 83%

Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1)

Logie

Lees

Allwood

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

AimRecently we have observed differences in the ability of metformin and AICAR to repress glucose production from hepatocytes using 8CPT‐cAMP. Previous results indicate that, in addition to activating protein kinase A, 8CPT‐modified cAMP analogues suppress the nitrobenzylthioinosine (NBMPR)‐sensitive equilibrative nucleoside transporter ENT1. We aimed to exploit 8CPT‐cAMP, 8CPT‐2‐Methyl‐O‐cAMP and NBMPR, which is highly selective for a high‐affinity binding‐site on ENT1, to investigate the role of ENT1 in the liver‐specific glucose‐lowering properties of AICAR and metformin.MethodsPrimary mouse hepatocytes were incubated with AICAR and metformin in combination with cAMP analogues, glucagon, forskolin and NBMPR. Hepatocyte glucose production (HGP) and AMPK signalling were measured, and a uridine uptake assay with supporting LC‐MS was used to investigate nucleoside depletion from medium by cells.ResultsAICAR and metformin increased AMPK pathway phosphorylation and decreased HGP induced by dibutyryl cAMP and glucagon. HGP was also induced by 8CPT‐cAMP, 8CPT‐2‐Methyl‐O‐cAMP and NBMPR; however, in each case this was resistant to suppression by AICAR but not by metformin. Cross‐validation of tracer and mass spectrometry studies indicates that 8CPT‐cAMP, 8CPT‐2‐Methyl‐O‐cAMP and NBMPR inhibited the effects of AICAR, at least in part, by impeding its uptake into hepatocytes.ConclusionsWe report for the first time that suppression of ENT1 induces HGP. ENT1 inhibition also impedes uptake and the effects of AICAR, but not metformin, on HGP. Further investigation of nucleoside transport may illuminate a better understanding of how metformin and AICAR each regulate HGP.

show abstract

Section: Discussionmentioning

confidence: 83%

Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1)

Logie

Lees

Allwood

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study

Khorasanchi

Arabi

Akhavein

et al. 2016

JCDR

View full text Add to dashboard Cite

IntrOductIOnDipyridamole is a nucleoside transport inhibitor that augments endogenous adenosine [1]. Moreover, it inhibits phosphodiesterases and causes an increase in cellular content of cyclic Adenosine Monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) [2]. Dipyridamole is indicated for the induction of stress in myocardial scintigraphy [3].Adenosine plays an important role as a paracrine and/ or an autocrine hormone in a variety of physiological or pathophysiological processes including cardiovascular diseases and diabetes [4,5]. It acts by binding to adenosine receptors and influences glucose disposal, carbohydrate metabolism, lipolysis and insulin sensitivity [6,7], local blood flow [8], mean arterial pressure and heart rate [9]. Four adenosine receptors (A1, A2a, A2b, and A3) have been cloned and characterized in mammalian species. While A1 and A3 receptors are preferentially coupled to inhibitory G-proteins (Gi/o), the A2 receptors interact with stimulatory G-protein (Gs) [10]. Adenosine A3 receptors were found to produce cardioprotective effects during myocardial ischemia/ischemic reperfusion [10]. On the other hand, blockade of adenosine A1 receptors improves glucose tolerance in obese Zucker rats; these rats show a better profile of peak serum insulin level and areas under glucose curves, compared to untreated rats [11]. Yet, adenosine is not the sole mediator of dipyridamole pharmacological effects [12].It is noteworthy that the concentration of dipyridamole required to produce a significant effect on glycolytic rate (2µM) is much less than that required to exert a significant rise in intracellular and interstitial adenosine concentration in muscles (50µM) [12]. Dipyridamole reduces glucose-induced osteopontin expression in arterial vasculature, thereby decreasing the medial artery calcification and stiffness. This effect is mediated through inhibition of phosphodiesterase, and Reactive Oxygen Species (ROS) [2]. However, a net effect of dipyridamole in blood sugar during cardiac scintigraphy has been not investigated.Cardiovascular stress test using exercise or pharmacological agents has long been established as a diagnostic procedure in cardiovascular scintigraphy. In this regard, pharmacological stress is produced by dobutamine, dipyridamole, adenosine or regadenoson [13]. Dipyridamole inhibits intracellular reuptake and deamination of adenosine, thereby producing a vasodilatory effect on coronary arteries. Such an effect on coronary vasodilation is attenuated in diseased coronary arteries, showing a reduced coronary flow reserve and failure of dilation in response to the drug [14].The aim of this study was to evaluate the acute effect of dipyridamole on blood glucose in patients undergoing myocardial rest/stress scintigraphy using 99mTc-sestamibi. In addition, a potential alteration of the outcome of a radionuclide scan was explored. MAterIAls And MethOdsThis cross-sectional study was performed on 299 patients who were recruited from the Department of Nuclear Medicine of

show abstract

Effect of Dipyridamole on Blood Glucose and Liver Cyclic Amp Levels and Platelet Count During Endotoxaemia in Mice

Cited by 2 publications

References 12 publications

Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1)

Regulation of hepatic glucose production and AMPK by AICAR but not by metformin depends on drug uptake through the equilibrative nucleoside transporter 1 (ENT1)

Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study

Contact Info

Product

Resources

About