Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography.

Amherdt, M; Patel, Yogesh C.; Orci, Lelio

doi:10.1172/jci113225

Cited by 46 publications

(23 citation statements)

References 22 publications

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“…These results are in agreement with those of in vitro studies which also demonstrate a relatively greater effect of S-28 on pancreatic B cells (15,19). Recently, an inhibitory effect ofelevated postprandial S-28 levels on pancreatic exocrine secretion has been reported (P. Hildebrand, unpublished observation), so it is likely that the effects of S-28 released during nutrient absorption are not restricted to the pancreatic B-cell.…”

Section: Discussionsupporting

confidence: 91%

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A physiologic role for somatostatin 28 as a regulator of insulin secretion.

D’Alessio¹,

Sieber²,

Beglinger³

et al. 1989

J. Clin. Invest.

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Somatostatin 28 (S-28) is a peptide produced in the intestinal tract which rises in the circulation during nutrient absorption. We tested the hypothesis that S-28 regulates B-cell function by (a) studying the effects on insulin secretion of "physiologic" infusions of S-28 and (b) measuring insulin responses during elevated nutrient-stimulated endogenous S-28 levels. (a) Synthetic S-28 was infused on separate days into six healthy men at rates of 25 and 50 ng/kg per h which mimicked postprandial levels. Subjects were given a bolus of glucose (0.1 g/kg) after 120 min. Insulin responses during S-28 infusions were compared to a control study using a saline infusion in the same individuals. Glucose-stimulated insulin secretion was inhibited during the infusion of 50 ng/kg per h S-28 when compared to control (P < 0.05). (b) Insulin secretion during elevations of endogenous S-28 was studied in healthy men who received a bolus of 2.5 g arginine (n = 14) or 25 U of secretin (n = 8) 120 min after swallowing 50 g fat, or, on a separate day, an equivalent volume of water. S-28 levels rose significantly after fat ingestion but did not change after water. Arginine and secretin-stimulated insulin secretion was inhibited following ingestion of fat compared with intake of water (P < 0.05). Arginineenhanced glucagon secretion was not changed by fat ingestion. We conclude that elevations in plasma S-28 levels, occurring during the postprandial state, attenuate B-cell secretion and this peptide may be a physiologic modulator of nutrient-stimulated insulin release.

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Section: Discussionsupporting

confidence: 91%

“…However, S-28 is the more potent inhibitor of pancreatic B cells and binds to them more avidly than to A cells (15,18,19). Conversely, S-14 binds to and inhibits A cells preferentially (15,19).…”

Section: Introductionmentioning

confidence: 99%

A physiologic role for somatostatin 28 as a regulator of insulin secretion.

D’Alessio¹,

Sieber²,

Beglinger³

et al. 1989

J. Clin. Invest.

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“…Although Moldovan et al [26] reported that insulin secretion is inhibited by an SSTR2A selective analogue in isolated perfused human pancreas, this analogue (DC32-87) has been found not to be SSTR2 selective [5]. Pharmacological data also suggest that different SSTR subtypes are expressed in glucagon and insulin cells in the rat endocrine pancreas, with glucagon secretion being most sensitive to SSTR2-selective analogues and insulin secretion most sensitive to SSTR5-selective analogues in rats [27,28,29]. Recently Kumar et al [16] analyzed SSTR subtype specific expression in human pancreatic islets and found SSTR2 in insulin and glucagon cells, with insulin, glucagon, and somatostatin cells each expressing multiple SSTR isoforms.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Localization of Somatostatin Receptor Type 2A in Rat and Human Tissues.

et al. 2001

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Abstract.In this study, we elucidated the cellular localization of somatostatin receptor (SSTR) by immunohistochemistry using an antibody specific for SSTR type 2A (SSTR2A) in various organs of rat and human. SSTR2A expression was basically similar in rat and human, except in the pancreas and adrenal cortex. In the pituitary gland, the posterior lobe and the majority of growth hormone cells and some ACTH and TSH cells expressed SSTR2A. In rat adrenal gland, the zona glomerulosa strongly expressed SSTR2A, whereas zone-specific immunoreactivity was not observed in human.The adrenal medulla moderately expressed SSTR2A in both rat and human. SSTR2A immunoreactivity was observed in islet cells and some ductal cells in human pancreas, and also in acinar cells of rat pancreas. In gastrointestinal (GI) tract, the majority of crypt cells and nerve plexuses strongly expressed SSTR2A. The number of SSTR2A positive cells was much more than that of chromogranin A positive endocrine cells. In the kidney, the glomerular capillaries and collecting tubules, but not proximal tubules, showed immunoreactivity. Somatostatin regulates endocrine and exocrine functions and the growth inhibition of various organs, such as the pituitary gland, pancreas and gastrointestinal (GI) tract, by acting on the somatostatin receptor (SSTR) of target organs [1, 2]. Five types of SSTR genes have been cloned and were shown to produce 6 types of proteins [3, 4]; however, SSTR2B has been detected only in rat, but not in human tis-

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“…Using the technique of quantitative electron microscopic autoradiography, we have previously identified specific binding sites for radioiodinated somatostatin-14 (S-14), '1251-insulin, and '251-glucagon on neonatal islet B, A, and D cells in monolayer culture (22,23). We have extended these observations and now describe the internalization of each radioligand by the three islet cell types.…”

Section: Introductionmentioning

confidence: 88%

“…Monolayer cultures of dispersed islet cells from 3-d-old rats were established in plastic Petri dishes as previously described (22,23). The medium consisted of MEM with 10% heat-inactivated FCS.…”

Section: Methodsmentioning

confidence: 99%

Binding and internalization of somatostatin, insulin, and glucagon by cultured rat islet cells.

Amherdt

Patel²,

Orci³

1989

J. Clin. Invest.

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The pathways by which islet B, A, and D cells bind and internalize homologous (self) and heterologous (other) islet hormones were compared. I'25I-TyrjSomatostatin-14 (S-14), 1251-insulin, and 1251-glucagon were incubated with monolayer cultures of neonatal rat islet cells. Tissues were processed for quantitative electron microscopic autoradiography by the probability circle method coupled to morphometry. For all three radioligands and all three cell types surface labeling was rapidly followed by internalization of the radioligands into endocytotic vesicles. The further intracellular movement of the ligand occurred in a time-and temperature-related manner and depended on whether it was homologous or heterologous for the cell in question. We conclude that (a) each of the three radioligands is internalized by islet cells in a time-and temperature-dependent manner; (b) after initial internalization the further intracellular progression of the endocytosed radioligand occurs freely in cells heterologous for the radioligand but poorly in cells homologous for the radioligand; and (c) binding and endocytosis can be uncoupled from lysosomal degradation of ligand.

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Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography.

Abstract: Quantitative electron microscopic autoradiography was used for comparing the binding of labeled somatostatin-14 (S-14) and somatostatin-28 (S-28) to islet cells. Monolayer cultures of rat islet cells were incubated with or

Cited by 46 publications

References 22 publications

A physiologic role for somatostatin 28 as a regulator of insulin secretion.

A physiologic role for somatostatin 28 as a regulator of insulin secretion.

Immunohistochemical Localization of Somatostatin Receptor Type 2A in Rat and Human Tissues.

Binding and internalization of somatostatin, insulin, and glucagon by cultured rat islet cells.

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