Production, Action, and Degradation of Somatostatin

Patel, Yogesh C.; Galanopoulou, Aristea S.; Papachristou, Dimitrios N.

doi:10.1002/cphy.cp070209

Cited by 8 publications

(17 citation statements)

References 390 publications

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“…Further analysis of insulinopenic diabetic rats using streptozotocin has demonstrated an accumulation of SST peptides from the pancreas and upper gut [194]. It addition, the hyperplasia of δ-cells in the islet of diabetic patients has been associated with the loss of glucose receptors, which results in a two-to threefold production of SST in these organs [173]. Further implicating the importance of systemic SST-28 and SSTR5 in the regulation of insulin secretion and glucose homeostasis in diabetes is the fact that more than 30% of peripheral SST peptide is SST-28 and SSTR5 has 10-to 15-fold affinity specifically towards to SST-28.…”

Section: Sst and Sstrs In Type 1 Diabetesmentioning

confidence: 97%

“…SST immunoreactivity has been located in the brain, peripheral nervous system, enteric and submucosal nerve plexi of the gut, the delta cells of the endocrine pancreas, thyroid and lymphoid tissue such as that of the thymus, spleen and lymph nodes [115][116][117][118]. In all tissues, including that of tumors, SST acts as an inhibitory hormone [95,103,144,173]. In some diseases, such as cutaneous T-cell lymphomas (Hodgkin's disease and non-Hodgkin's lymphomas), granulomatous diseases (tuberculosis, carcoidosis and Wegener's granulomatosis), rheumatoid arthritis and perhaps thymic tumors, cells have been shown to express a high density of SST receptors that can be visualized using radiolabeled octreotide [170,174,175].…”

Section: Sst and Sstrs In Type 1 Diabetesmentioning

confidence: 99%

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Somatostatin receptors and autoimmune‐mediated diabetes

Wang

Norman

Brunicardi

2004

Diabetes Metabolism Res

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Somatostatin (SST) peptide is produced by various SST-secreting cells throughout the body and acts as a neurotransmitter or paracrine/autocrine regulator in response to ions, nutrients, peptides hormones and neurotransmitters. SST is also widely distributed in the periphery to regulate the inflammatory and immune cells in response to hormones, growth factors, cytokines and other secretive molecules. SST peptides are considered the most important physiologic regulator of the islet cell, gastrointestinal cell and immune cell functions, and the importance of SST production levels has been implicated in several diseases including diabetes. The expression of SST receptors has also been found in T lymphocytes and primary immunologic organs. Interaction of SST and its receptors is also involved in T-cell proliferation and thymocyte selection. SSTR gene-ablated mice developed diabetes with morphologic, physiologic and immunologic alterations in the endocrine pancreas. Increased levels of mononuclear cell infiltration of the islets are associated with the increased levels of antigen-presenting cells located in the islets and peripancreatic lymph nodes. Increased levels of SST were also found in antigen-presenting cells and are associated with a significant increase of CD8 expression levels on CD4(+)/CD8(+) immature thymocytes. These findings highlight the crucial role of this neuroendocrine peptide and its receptors in regulating autoimmune functions.

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Section: Sst and Sstrs In Type 1 Diabetesmentioning

confidence: 97%

Section: Sst and Sstrs In Type 1 Diabetesmentioning

confidence: 99%

Somatostatin receptors and autoimmune‐mediated diabetes

Wang

Norman

Brunicardi

2004

Diabetes Metabolism Res

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“…It also has been shown that the cellular composition and location of cell types within the islets vary during development. 6 For example, C-cells constitute 40% of islet cells in the fetus and neonate, whereas the adult pancreas consists of 10% >-cells, 70% A-cells, 15% PP cells, and only 5% C-cells. 7,8 Delta cells have a granular appearance and have cytoplasmic processes that abut on islet capillaries.…”

Section: Pancreasmentioning

confidence: 99%

“…It is unknown whether a common or different mechanism activates the gene in different tissues. 6 In mice, the SST gene is first expressed on day 15 of embryonic development in cells that coexpress insulin, that is, later than the expression of glucagon (day 10) and insulin (day 12) genes. Insulin gene expression is later suppressed in cells that become mature SST-secreting C-cells.…”

Section: Somatostatinmentioning

confidence: 99%

“…94 95 SST-14, SST-28, and synthetic SST analogues act as inhibitory hormones in numerous tissues to regulate a wide range of physiological processes such as glandular secretion, neurotransmission, smooth muscle contractility, nutrient absorption, and cell division. 6 SST has widespread effects on the immune system including T-cell proliferation, lymphocyte adhesion, cytokine production, and natural killer activity, which are thought to be involved in the pathogenesis of type 1 diabetes. 96,97 SST secretion is influenced by many different agents such as ions, nutrients, neurotransmitters, hormones, growth factors, and cytokines.…”

Section: Somatostatinmentioning

confidence: 99%

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Somatostatin and its Receptors in the Development of the Endocrine Pancreas

Ballian

Brunicardi²,

Wang³

2006

Pancreas

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The development of the endocrine pancreas is regulated by numerous transcription and growth factors. Somatostatin (SST) is present in many tissues and acts as a neurotransmitter and autocrine/paracrine/endocrine regulator in response to ions, nutrients, peptides, and hormones as well as neurotransmitters. In the pancreas, there is evidence that SST acts an inhibitory paracrine regulator of hormone secretion. Somatostatin receptors (SSTRs) are a family of 5 transmembrane G protein-coupled receptors, which are widely expressed in mammals including humans. SSTRs regulate multiple downstream signal transduction pathways that mediate inhibitory effects. These receptors also exhibit age- and tissue-specific expression patterns. Interactions of SST and SSTRs are not only important during normal pancreas development, but have also been implicated in many pancreatic diseases such as diabetes mellitus and pancreatic cancer. In this review article, we use evidence from recently published animal studies to present the critical roles of SST and SSTRs proteins in the development of the endocrine pancreas.

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SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

et al. 2005

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Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (bSSTR5 Kd ) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, bSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the bSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in bSSTR5Kd mice pancreata. In addition, bSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in bSSTR5Kd mice. Further studies of bSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.

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Production, Action, and Degradation of Somatostatin

Abstract: The sections in this article are: Anatomical Distribution of Somatostatin Cells Localization Pancreatic Somatostatin Cells Biosynthesis, Processing, and Intracellular Targeting Somatostatin Genes and Gene Products Regulation of Islet Somatostatin Regulation of Secretion … Show more

Cited by 8 publications

References 390 publications

Somatostatin receptors and autoimmune‐mediated diabetes

Somatostatin receptors and autoimmune‐mediated diabetes

Somatostatin and its Receptors in the Development of the Endocrine Pancreas

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

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