Molecular cloning of the human type VIII adenylyl cyclase

Defer, Nicole; Marinx, Olivier; Stengel, Dominique; Danisova, Alena; Iourgenko, Vadim; Matsuoka, Isao; Caput, Daniel; Hanoune, Jacques

doi:10.1016/0014-5793(94)00836-1

Cited by 38 publications

(25 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ADCY8 is clearly expressed to a comparable extent in pancreatic β-cells in rodents and in humans although levels are low as reported previously [6]. Expression of ADCY8 in human islets has also been reported most recently using a primer different from ours [29] and the long-known existence of splice variants [36] may explain its reported absence in certain studies.…”

Section: Discussionmentioning

confidence: 70%

Multilevel control of glucose homeostasis by adenylyl cyclase 8

et al. 2014

View full text Add to dashboard Cite

Aims/hypothesis Nutrient homeostasis requires integration of signals generated by glucose metabolism and hormones. Expression of the calcium-stimulated adenylyl cyclase ADCY8 is regulated by glucose and the enzyme is capable of integrating signals from multiple pathways. It may thus have an important role in glucose-induced signalling and glucose homeostasis. Methods We used pharmacological and genetic approaches in beta cells to determine secretion and calcium metabolism. Furthermore, Adcy8 knockout mice were characterised. Results In clonal beta cells, inhibitors of adenylyl cyclases or their downstream targets reduced the glucose-induced increase in cytosolic calcium and insulin secretion. This was reproduced by knock-down of ADCY8, but not of ADCY1. These agents also inhibited glucose-induced increase in cytosolic calcium and electrical activity in primary beta cells and similar effects were observed after ADCY8 knock-down.Moreover, insulin secretion was diminished in islets from Adcy8 knockout mice. These mice were glucose intolerant after oral or intraperitoneal administration of glucose whereas their levels of glucagon-like peptide-1 remained unaltered. Finally, we knocked down ADCY8 in the ventromedial hypothalamus to evaluate the need for ADCY8 in the central regulation of glucose homeostasis. Whereas mice fed a standard diet had normal glucose levels, high-fat diet exacerbated glucose intolerance and knock-down mice were incapable of raising their plasma insulin levels. Finally we confirmed that ADCY8 is expressed in human islets. Conclusions/interpretations Collectively, our findings demonstrate that ADCY8 is required for the physiological activation of glucose-induced signalling pathways in beta cells, for glucose tolerance and for hypothalamic adaptation to a high-fat diet via regulation of islet insulin secretion.Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3445-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

show abstract

Section: Discussionmentioning

confidence: 70%

Multilevel control of glucose homeostasis by adenylyl cyclase 8

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Oligonucleotide primers specifically designed to be complementary to the cDNA sequence of human ACs, rather than rat, murine or bovine sequences, have been employed to demonstrate the presence of mRNA encoding for a variety of AC isoforms. At present, human sequence data exist for only five AC isoforms, namely AC I (Villacres et al 1993), AC II (Stengel et al 1992), AC III (Yang et al 1999), AC VIII (Defer et al 1994) and AC IX (Hacker et al 1998). By utilising primers based on these published human sequences we have demonstrated the presence of mRNA encoding for Groups 1 (types I, III and VIII), 2 (AC II) and 4 (AC IX) in both pregnant and non-pregnant human myometrium.…”

Section: Discussionmentioning

confidence: 85%

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Price

Pochun²,

Phaneuf³

et al. 2000

Journal of Endocrinology

View full text Add to dashboard Cite

The precise factors involved in the transition of the relaxed pregnant uterus to the contractile state at the onset of parturition remain unclear, but it is accepted that cAMPgenerating pathways contribute to uterine relaxation. We have previously reported an increased expression of the adenylyl cyclase (AC)-stimulating protein G s in human myometrium during gestation, with a corresponding increase in GTP-stimulated AC activity. However, little is known about the predominating AC isoforms expressed during pregnancy. This information is important, because although all AC isoforms are stimulated by G s, their regulation by other signalling molecules is very different. In the present study we have identified the isoforms of AC expressed in both pregnant and non-pregnant myometrium by mRNA analysis and immunoblotting. mRNA encoding for AC I, II, III, VIII and IX was present in non-pregnant and pregnant myometrium, and in cultured myometrial cells. Differing levels of AC protein could be detected in myometrial plasma membranes, with decreased levels of Group 1 (isoforms I, III and VIII) and Group 4 (IX) ACs allied with increased levels of Group 2 (II, IV and VII) and 3 (V and VI) ACs during pregnancy. These findings imply a role for Group 2-activating pathways, e.g. G-protein -subunits and protein kinase C, in the maintenance of uterine quiescence, whilst suggesting a lesser involvement of calcium-calmodulin complex, an activator of Group 1 AC isoforms, in uterine relaxation during gestation. These data may provide an alternative pharmacological approach for the attenuation of preterm labour.

show abstract

“…15 Mice were screened for the presence of the transgene by Southern blot performed on tail genomic DNA. Two founders were identified and propagated by crossbreeding with C57BL/6 wild-type mice.…”

Section: Generation Of Transgenic Micementioning

confidence: 99%

“…12 In contrast, AC1 and AC8, which are essentially expressed in the central nervous system, are activated by Ca 2ϩ through the Ca 2ϩ /calmodulin complex. [13][14][15] In this study, we describe transgenic mice overexpressing the Ca 2ϩ /calmodulin-activatable isoform AC8 specifically targeted to cardiomyocytes. Surprisingly, we observed that AC8 overexpression has no effect on the viability of the animals but leads to a higher basal intrinsic contractility that is unresponsive to further ␤-AR stimulation.…”

mentioning

confidence: 99%

Enhanced Cardiac Function in Transgenic Mice Expressing a Ca ²⁺ -Stimulated Adenylyl Cyclase

Lipskaia¹,

Defer²,

Esposito³

et al. 2000

Circulation Research

Self Cite

View full text Add to dashboard Cite

Abstract-The predominant functional adenylyl cyclases normally expressed in cardiac tissue and coupled to ␤-adrenergic receptors are inhibited by micromolar Ca 2ϩ concentration. To modify the overall balance of activities, we have generated transgenic mice expressing the Ca 2ϩ -stimulatable adenylyl cyclase type 8 (AC8) specifically in the heart. AC activity is increased by at least 7-fold in heart membranes from transgenic animals and is stimulated by Ca 2ϩ in the same range of concentration that inhibits the endogenous activity. Moreover, the in vivo basal protein kinase A activity was augmented 4-fold. Overexpression of AC8 in the heart has no detrimental consequences on global cardiac function. Basal heart rate and contractile function, measured by noninvasive echocardiography, were unchanged. In contrast, on release of parasympathetic tone, the intrinsic contractility is heightened and unresponsive to further ␤-adrenergic receptor stimulation. AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca

show abstract

Molecular cloning of the human type VIII adenylyl cyclase

Cited by 38 publications

References 32 publications

Multilevel control of glucose homeostasis by adenylyl cyclase 8

Multilevel control of glucose homeostasis by adenylyl cyclase 8

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Enhanced Cardiac Function in Transgenic Mice Expressing a Ca ²⁺ -Stimulated Adenylyl Cyclase

Contact Info

Product

Resources

About

Molecular cloning of the human type VIII adenylyl cyclase

Cited by 38 publications

References 32 publications

Multilevel control of glucose homeostasis by adenylyl cyclase 8

Multilevel control of glucose homeostasis by adenylyl cyclase 8

Adenylyl cyclase isoforms in pregnant and non-pregnant human myometrium

Enhanced Cardiac Function in Transgenic Mice Expressing a Ca 2+ -Stimulated Adenylyl Cyclase

Contact Info

Product

Resources

About

Enhanced Cardiac Function in Transgenic Mice Expressing a Ca ²⁺ -Stimulated Adenylyl Cyclase