Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects.

Harris, Alan G.

doi:10.1136/gut.35.3_suppl.s1

Cited by 247 publications

(168 citation statements)

References 38 publications

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“…Octreotide injection promptly diminished serum GH but this suppressive effect was limited, as subsequent injections did not produce further reduction in serum GH. Since elimination half life of a single subcutaneous dose was estimated at about 1.5 h [16], repeated injections of 100 jig octreotide at meal times appeared to be sufficient to prolong the suppression of serum GH and to prevent the diurnal GH elevation in the evening hours as seen by our results (Figs. 1B and 1C) but was probably insufficient through the night hours.…”

Section: Discussionsupporting

confidence: 65%

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Chang

Kuo

Fang³

et al. 1996

Endocr J

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Abstract. To study GH response to the long-acting somatostatin analogue, we treated 11 actively acromegalic patients with octreotide (Sandostatin),100 µg, sc, tid, for six months. Their endocrinological outcomes and clinical improvements varied. The 11-h GH secretory profiles on pretreatment day confirmed the hypersecretion of GH in all patients. Three hours after the first dose of octreotide, serum GH declined rapidly to levels below 5 ng/ml in all but two patients who failed to normalize their serum GH. In spite of the subsequent doses, there was no further suppression in serum GH. Drug resistance with GH rebound developed in some patients after three months of continued treatment.The paradoxical serum GH rises in response to oral glucose or iv TRH detected before the treatment in all patients attenuated or disappeared after the 6-month octreotide therapy; an exceptional case was one of the above-mentioned two patients, whose serum GH was stimulated more than before by glucose and TRH at the end of therapy. Serum insulin-like growth factor I (IGF-I) levels of all patients showed a significant reduction after 6-month treatment, but their mean values remained abnormally high. There were no intolerable adverse side effects; some patients, however, experienced pain at the injection site, passage of loose stool, and incidence of new gall stone or intrahepatic lesions on octreotide therapy. We concluded that octreotide was a useful long-term adjunctive therapeutic agent for patients with active acromegaly, but that a high degree of response heterogeneity including total refractoriness would be expected.

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Section: Discussionsupporting

confidence: 65%

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Chang

Kuo

Fang³

et al. 1996

Endocr J

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“…Thus, GLP-1, an ''incretin,'' is stimulated by nutrient ingestion and is a positive modulator of insulin secretion (1). Somatostatin-28, a ''decretin,'' is also stimulated by nutrient ingestion but is a negative modulator of insulin secretion (32,33). The data presented here suggest another longer-term modulation of islet ␤ cell function by the liver.…”

Section: Discussionmentioning

confidence: 68%

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

Zhao

Teague

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

138

115

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Both insulin and insulin-like growth factor 1 (IGF-1) are known to reduce glucose-dependent insulin secretion from the ␤ cells of pancreatic islets. In this paper we show that the mechanism by which IGF-1 mediates this effect is in large part through activation of a specific cyclic nucleotide phosphodiesterase, phosphodiesterase 3B (PDE3B). More specifically, in both isolated pancreatic islets and insulin-secreting HIT-T15 cells, IGF-1 inhibits insulin secretion that has been increased by glucose and glucagonlike peptide 1 (GLP-1). Moreover, IGF-1 decreases cAMP levels in parallel to the reduction of insulin secretion. Insulin secretion stimulated by cAMP analogs that activate protein kinase A and also are substrates for PDE3B is also inhibited by IGF-1. However, IGF-1 does not inhibit insulin secretion stimulated by nonhydrolyzable cAMP analogs. In addition, selective inhibitors of PDE3B completely block the ability of IGF-1 to inhibit insulin secretion. Finally, PDE3B activity measured in vitro after immunoprecipitation from cells treated with IGF-1 is higher than the activity from control cells. Taken together with the fact that pancreatic ␤ cells express little or no insulin receptor but large amounts of IGF-1 receptor, these data strongly suggest a new regulatory feedback loop model for the control of insulin secretion. In this model, increased insulin secretion in vivo will stimulate IGF-1 synthesis by the liver, and the secreted IGF-1 in turn feedback inhibits insulin secretion from the ␤ cells through an IGF-1 receptormediated pathway. This pathway is likely to be particularly important when levels of both glucose and secretagogues such as GLP-1 are elevated.

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“…Octreotide is an eight-amino acid analogue of somatostatin with four identical amino acids, with a longer halflife and greater affinity for SSRT2, SSRT3 and SSRT5, which makes a safe and sensitive imaging modality for the detection of gastroenteropancreatic neuroendocrine tumors [29,30] . Since then, octreotide derivatives have been developed, allowing stable labeling with radiometals, as well as increased affinity for somatostatin receptor as compared with Octreoscan …”

Section: Scintigraphymentioning

confidence: 99%

Exploring new frontiers in molecular imaging: Emergence of⁶⁸Ga PET/CT

Tan

Goh²

2010

WJR

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Since US Food and Drug Administration approval of 18-fluorodeoxyglucose as a positron tracer, and the development of hybrid positron emission tomography/ computed tomography machines, there has been a great increase in clinical application and progress in the field of nuclear molecular imaging. However, not underestimating the value of 18 F, there are known limitations in the use of this cyclotron-produced positron tracer. We hence turn our focus to an emerging positron tracer, 68 Ga, and examine the advantages, current clinical uses and potential future applications of this radioisotope. THE DEVELOPMENT OF POSITRON EMISSION TOMOGRAPHYPositron emission tomography (PET) imaging is essentially a story of a technique in wait of a technology. Since the discovery of positron emission in 1933 by Thibaud and Joliot et al, and the subsequent report of the coincident nature of emissions by Klemperer and Beringer, it has in effect taken close to half a century for the full realization of PET imaging in mainstream medical practice [1] . The history of PET development is a fascinating look into the technological advances in molecular medicine, and the account of Terry Jones provides fascinating reading [1] . The first use of positron tracers was likely performed in the 1940s using 11 CO in animal models [2] , with its first possible use in humans performed in the 1950s at the Hammersmith Hospital in London, United Kingdom using 15 O2 in studies of lung ventilation [3] . This was followed by increasing use of positron tracers in the physiological assessment of lung function, which resulted in the installation of the world's first hospital-based cyclotron in 1955. Subsequently, development shifted into myocardial perfusion [4] , cerebral perfusion [5][6][7] , and of course, glucose metabolism [8][9][10][11] . This development in positron tracers mirrored the progress in positron imaging. In the 1970s, Massachusetts General Hospital developed, what was then, the most advanced coincidence positron camera system, with a spatial resolution of approximately 1 cm [12] . This was followed by developments predominantly in single photon emission computed tomography (SPECT) with work done by Kuhl, Budinger and Gullberg, and in 1974, there were reports of the development of a dedicated single-plane positron emission transaxial tomograph, which was the precursor to the current PET systems.These developments explain the slow implementation of PET into clinical practice, as synchronous developments in both tracer and detector technology were reWorld Journal of Radiology W J R

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Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects.

Cited by 247 publications

References 38 publications

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

Exploring new frontiers in molecular imaging: Emergence of⁶⁸Ga PET/CT

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Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects.

Cited by 247 publications

References 38 publications

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Heterogeneous Responses to the Long-Term Treatment of Active Acromegaly with Octreotide.

Attenuation of insulin secretion by insulin-like growth factor 1 is mediated through activation of phosphodiesterase 3B

Exploring new frontiers in molecular imaging: Emergence of68Ga PET/CT

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Exploring new frontiers in molecular imaging: Emergence of⁶⁸Ga PET/CT