Function and expression of somatostatin receptors of the endocrine pancreas

Strowski, Mathias Z.; Blake, Allan D.

doi:10.1016/j.mce.2008.02.007

Cited by 80 publications

(64 citation statements)

References 157 publications

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“…In mammals, it has been shown that SS-14 and SS-28 differentially target pancreatic a-or b-cells. In accordance with this, SS-14, which is locally produced by d-cells, has been reported to be associated with the inhibition of glucagon secretion, while circulating SS-28 seems to primarily inhibit insulin secretion (Strowski & Blake 2008). In rodents, glucagon inhibition is mediated by SSTR2, while insulin inhibition involves STTR5.…”

Section: Ss-ergic Systemsmentioning

confidence: 53%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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Somatostatin (SS) and urotensin II (UII) are members of two families of structurally related neuropeptides present in all vertebrates. They exert a large array of biological activities that are mediated by two families of G-protein-coupled receptors called SSTR and UTS2R respectively. It is proposed that the two families of peptides as well as those of their receptors probably derive from a single ancestral ligand-receptor pair. This pair had already been duplicated before the emergence of vertebrates to generate one SS peptide with two receptors and one UII peptide with one receptor. Thereafter, each family expanded in the three whole-genome duplications (1R, 2R, and 3R) that occurred during the evolution of vertebrates, whereupon some local duplications and gene losses occurred. Following the 2R event, the vertebrate ancestor is deduced to have possessed three SS (SS1, SS2, and SS5) and six SSTR (SSTR1-6) genes, on the one hand, and four UII (UII, URP, URP1, and URP2) and five UTS2R (UTS2R1-5) genes, on the other hand. In the teleost lineage, all these have been preserved with the exception of SSTR4. Moreover, several additional genes have been gained through the 3R event, such as SS4 and a second copy of the UII, SSTR2, SSTR3, and SSTR5 genes, and through local duplications, such as SS3. In mammals, all the genes of the SSTR family have been preserved, with the exception of SSTR6. In contrast, for the other families, extensive gene losses occurred, as only the SS1, SS2, UII, and URP genes and one UTS2R gene are still present.

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Section: Ss-ergic Systemsmentioning

confidence: 53%

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Tostivint¹,

Daza²,

Bergqvist³

et al. 2014

Journal of Molecular Endocrinology

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“…This fact may affect the length of primary cilia: short primary cilia on GH cells is enough for sensing. The use of SSTR subtype-selective drugs and gene-knockout studies suggest that the inhibition of insulin secretion by somatostatin is mediated predominantly by SSTR1 and SSTR5 in rodents (32,33,36). An in vitro study of human pancreatic islets also reported that somatostatin inhibited both insulin and glucagon release through SSTR1, SSTR2, and SSTR5 (30).…”

Section: Discussionmentioning

confidence: 99%

Restricted expression of somatostatin receptor 3 to primary cilia in the pancreatic islets and adenohypophysis of mice

2011

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The primary cilium is now considered to function as a fundamental, not rudimentary, structure for mechanical and chemical sensing by individual cells. Primary cilia in neurons express type III adenylyl cyclase (ACIII) and GPCRs for somatostatin (somatostatin receptor 3, SSTR3), serotonin, and melanin-concentrating hormone. The present immunohistochemical and electron microscopic study revealed an abundant occurrence of SSTR3-expressing solitary cilia in insulin-and growth hormone-secreting cells of the mouse. The SSTR3 immunoreactivity was restricted to the plasma membrane of cilia in both cell types, differing from previously reported immunohistochemical localization of SSTRs to cell bodies. The primary cilia in the islet cells were longer than those in the pituitary cells and extended for a long distance in the intercellular canalicules endowed with microvilli. No other endocrine organs were provided with the SSTR3-expressing primary cilia, while the primary cilia in these organs were frequently immunolabeled with ACIII antibody. Since the somatostatin inhibition of both insulin and GH release is regulated mainly by SSTR1 and SSTR5, the primary cilia expressing SSTR3 may be involved in a signaling which differs from that via other SSTR subtypes expressing in cell bodies.

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“…The clinically available SSA, Octreotide and Lanreotide respectively, significantly suppress GH secretion in up to 50-70% of acromegalic patients (2,3,4) while strict biochemical control (GH !1 mg/l) is achieved in up to 33% (3). However, these SSA also suppress insulin secretion and thus negatively affect glucose homoeostasis in a significant number of patients (3,5,6,7,8).…”

Section: Introductionmentioning

confidence: 99%

DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours

Plöckinger

Hoffmann²,

Geese³

et al. 2012

European Journal of Endocrinology

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Objective: Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin-suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide. Methods: Twenty-seven hSA were characterised immunohistochemically for their hormone-and sstexpression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time-(nZ6) and dose-response (nZ21) experiments. A positive response was defined as GH suppression to below 80% of baseline. Results: In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC 50 were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (nZ6) nor tumour morphology was related to the GH response. However, semiquantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression. Conclusions: DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide.

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Function and expression of somatostatin receptors of the endocrine pancreas

Abstract: DisclosureThe authors have nothing to disclose Acknowledgment MZS was supported by a research grant from the Deutsche Forschungsgemeinschaft (STR558/4-1 and 4-2) and the Sonnenfeld-Stiftung.

Cited by 80 publications

References 157 publications

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

MOLECULAR EVOLUTION OF GPCRS: Somatostatin/urotensin II receptors

Restricted expression of somatostatin receptor 3 to primary cilia in the pancreatic islets and adenohypophysis of mice

DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5-selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours

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