Purinergic receptors and metabolic function

Petit, Pierre; Loubatires-Mariani, M. M.; Keppens, Stefaan; Sheehan, Michael J.

doi:10.1002/(sici)1098-2299(199611/12)39:3/4<413::aid-ddr23>3.0.co;2-0

Cited by 12 publications

(4 citation statements)

References 57 publications

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“…ATP from the insulin secretory granules and adenosine formed by extracellular ATP degradation are other putative amplifiers of glucagon secretion. The well-established stimulatory effect of adenosine is mediated by cAMP-elevating A 2 receptors ( 50 , 61 , 62 ), whereas direct ATP actions on Ca 2+ -elevating P2Y 1 purinoceptors have been claimed either to stimulate ( 51 ) or to inhibit ( 50 ) glucagon release. A particularly interesting aspect of P2Y 1 purinoceptor signalling is that it can mediate synchronization of the insulin secretion-generating [Ca 2+ ] i oscillations among dispersed β-cells ( 63 ) and pancreatic islets ( 64 ) that lack physical contact.…”

Section: Paracrine Control Of Glucagon Releasementioning

confidence: 99%

Glucose control of glucagon secretion—‘There’s a brand-new gimmick every year’

Gylfe

2016

Upsala Journal of Medical Sciences

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Glucagon from the pancreatic α-cells is a major blood glucose-regulating hormone whose most important role is to prevent hypoglycaemia that can be life-threatening due to the brain’s strong dependence on glucose as energy source. Lack of blood glucose-lowering insulin after malfunction or autoimmune destruction of the pancreatic β-cells is the recognized cause of diabetes, but recent evidence indicates that diabetic hyperglycaemia would not develop unless lack of insulin was accompanied by hypersecretion of glucagon. Glucagon release has therefore become an increasingly important target in diabetes management. Despite decades of research, an understanding of how glucagon secretion is regulated remains elusive, and fundamentally different mechanisms continue to be proposed. The autonomous nervous system is an important determinant of glucagon release, but it is clear that secretion is also directly regulated within the pancreatic islets. The present review focuses on pancreatic islet mechanisms involved in glucose regulation of glucagon release. It will be argued that α-cell-intrinsic processes are most important for regulation of glucagon release during recovery from hypoglycaemia and that paracrine inhibition by somatostatin from the δ-cells shapes pulsatile glucagon release in hyperglycaemia. The electrically coupled β-cells ultimately determine islet hormone pulsatility by releasing synchronizing factors that affect the α- and δ-cells.

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Section: Paracrine Control Of Glucagon Releasementioning

confidence: 99%

Glucose control of glucagon secretion—‘There’s a brand-new gimmick every year’

Gylfe

2016

Upsala Journal of Medical Sciences

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“…The activation of these receptors elicited a strong and long lasting potentiation of the insulin secretion induced by a slightly stimulating glucose concentration. The pharmacological properties and physiological relevance of purinergic receptors of the pancreatic B cell have been reviewed elsewhere (Hillaire‐Buys et al , 1994; Loubatières‐Mariani et al , 1995; 1997; Petit et al , 1996). Recently, a cDNA clone encoding a rat P2Y receptor was isolated from an insulinoma cDNA library (Tokuyama et al , 1995).…”

Section: Introductionmentioning

confidence: 99%

Evidence for two different types of P2 receptors stimulating insulin secretion from pancreatic B cell

Petit

Hillaire‐Buys

Manteghetti

et al. 1998

British J Pharmacology

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1 Adenine nucleotides have been shown to stimulate insulin secretion by acting on P2 receptors of the P2Y type. Since there have been some discrepancies in the insulin response of di erent analogues of ATP and ADP, we investigated whether two di erent types of P2 receptors exist on pancreatic B cells. The e ects of a,b-methylene ATP, which is more speci®c for the P2X subtype, were studied in vitro in pancreatic islets and isolated perfused pancreas from rats, in comparison with the potent P2Y receptor agonist ADPbS. 2 In isolated islets, incubated with a slightly stimulating glucose concentration (8.3 mM), a,b-me ATP (200 mM) and ADPbS (50 mM) similarly stimulated insulin secretion; by contrast, under a non stimulating glucose concentration (3 mM), a,b-me ATP was still e ective whereas ADPbS was not. In the same way, in islets perifused with 3 mM glucose, a,b-me ATP but not ADPbS induced a partial but signi®cant reduction in the peak 86 Rb e ux induced by the ATP-dependent potassium channel opener diazoxide. 3 In the isolated pancreas, perfused with a non stimulating glucose concentration (4.2 mM), ADPbS and a,b-me ATP (5 ± 50 mM), administered for 10 min, induced an immediate, transient and concentration-dependent increase in the insulin secretion; their relative potency was not signi®cantly di erent. In contrast, with a slightly stimulating glucose concentration (8.3 mM), ADPbS was previously shown to be 100 fold more potent than a,b-me ATP. Furthermore, at 4.2 mM glucose a second administration of a,b-me ATP was ine ective. In the same way, ADPbS was also able to desensitize its own insulin response. At 3 mM glucose, a,b-me ATP as well as ADPbS (50 mM) induced a transient stimulation of insulin secretion and down regulated the action of each other. 4 These results give evidence that pancreatic B cells, in addition to P2Y receptors, which potentiate glucose-induced insulin secretion, are provided with P2X receptors, which transiently stimulate insulin release at low non-stimulating glucose concentration and slightly a ect the potassium conductance of the membrane.

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“…Besides its well-established roles in central and peripheral neuro-transmission (Dunwiddie et al, 1996), recent evidence has implicated adenosine in the modulation of neuro-endocrine-immune system function (Prabhakar et al, 1995;Thiel and Chouker, 1995;Petit et al, 1996), and in the induction of cell death (Abbracchio, 1996;Abbracchio et al, 1997;Jacobson, 1998;Jacobson et al, 1999). Adenosine analogs (in particular 2Ј-deoxyderivatives) may indeed act as effective antitumoral agents (Carson et al, 1984;Cheson, 1995).…”

mentioning

confidence: 99%

Apoptosis induced by 2-chloro-adenosine and 2-chloro-2′-deoxy-adenosine in a human astrocytoma cell line: Differential mechanisms and possible clinical relevance

et al. 2000

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We have previously demonstrated that 2-chloro-adenosine (2-CA) can induce apoptosis of rat astroglial cells (Abbracchio et al. [1995] Biochem. Biophys. Res. Commun. 213:908-915). In the present study, we have characterized, for the first time, the effects induced on a human astrocytoma cell line (ADF cells) by both 2-CA and its related analog 2-chloro-2'-deoxy-adenosine (2-CdA, that is employed as anti-cancer agent in chronic lymphoid malignancies). Exposure of these cells to either adenosine analog resulted in time- and concentration-dependent apoptosis. Experiments with pharmacological agents known to interfere with adenosine receptors, its membrane transporter, and intracellular nucleoside kinases showed that: (i) cell death induced by either adenosine analog did not depend on extracellular adenosine receptors, but on a direct intracellular action; however, only in the case of 2-CA, was entry into cells mediated by the specific nitrobenzyl-tioinosine-sensitive transporter; (ii) for both adenosine analogs, induction of apoptosis required the phosphorylation/activation by specific intracellular nucleoside kinases, i.e., adenosine kinase for 2-CA, and deoxycytidine kinase for 2-CdA. In addition, only in the case of 2-CdA, was induction of apoptosis preceded by a block of cells at the G2/M phase of the cell cycle. Finally, at concentrations of either analog that killed about 80-90% of astrocytoma cells, a significantly lower effect on the viability of primary cortical neurons was observed. In conclusion, both adenosine analogs can trigger apoptosis of human astrocytoma cells, albeit with different mechanisms. This effect together with the relative sparing of neuronal cells, may have potential clinical implications for the therapy of tumors of glial origin.

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Purinergic receptors and metabolic function

Cited by 12 publications

References 57 publications

Glucose control of glucagon secretion—‘There’s a brand-new gimmick every year’

Glucose control of glucagon secretion—‘There’s a brand-new gimmick every year’

Evidence for two different types of P2 receptors stimulating insulin secretion from pancreatic B cell

Apoptosis induced by 2-chloro-adenosine and 2-chloro-2′-deoxy-adenosine in a human astrocytoma cell line: Differential mechanisms and possible clinical relevance

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