Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the characteristics of lysosomes in rat islet endocrine cells, we examined the precise localization of cathepsins B, H, and L and their specific inhibitors, cystatins alpha and beta, using immunocytochemical techniques. By use of serial semi-thin sections, we detected immunoreactivity for cathepsin B in insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-positive (PP) cells. Strong immunoreactivity for cathepsin H was seen in A-cells and weak immunoreactivity in PP cells, but none in others. Immunodeposits for cystatin beta were demonstrated in B-cells. Brief dipping of thin sections in 1% sodium methoxide before the following immunocytochemical reaction enhanced specific deposits of immunogold particles on the target organelles. Use of a double-immunostaining technique showed co-localization of insulin with cystatin beta in many secretory granules. This suggests that cystatin beta may regulate converting enzymes participating in the maturation process of insulin. By use of an immunogold technique, heterogeneous localization of cathepsins B and H in lysosomes was also found among islet cells at the light microscopic level. This may be due to the difference in peptides degraded in lysosomes among the cells.
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PMID:Immunocytochemical localization of cathepsins B, H, and their endogenous inhibitor, cystatin beta, in islet endocrine cells of rat pancreas. 329 Mar 33

An extract of a neuroendocrine tumor of the human pancreas contained a high concentration of insulin and the C-peptide of proinsulin, as determined by radioimmunoassay, together with somatostatin, calcitonin, and thymosin beta 4. Analysis of the molecular forms of the proinsulin-derived peptides by high-performance liquid chromatography demonstrated that insulin was stored in the tumor as the intact peptide. In contrast, metabolites of C-peptide, representing the (1-21), (1-23), (1-25) and (1-29) N-terminal fragments, were isolated from the extract in addition to intact C-peptide. Generation of these metabolites involves cleavage of Xaa-Leu or Leu-Xaa bonds. Previous immunohistochemical studies have identified cathepsin B in secretory granules and lysosomes of human insulinoma cells. Synthetic human C-peptide was rapidly cleaved by purified human cathepsin B, primarily at the site of leucine residues, to give several metabolites, including the (1-25) and (1-23) fragments. The data indicate that the C-peptide of proinsulin is selectively metabolized in the neoplastic B cell by a mechanism that involves proteolytic cleavages in the C-terminal region of the peptide.
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PMID:Intracellular degradation of the C-peptide of proinsulin, in a human insulinoma: identification of sites of cleavage and evidence for a role for cathepsin B. 771 41

Radioligand targeting of somatostatin receptor subtype 2 (sstr2)-positive tumors with synthetic somatostatin analogues such as octreotide is subject to improvement in tumor to nontumor biodistribution, in part because internalization of such somatostatin analogues is limited by sstr2 recycling to the cell surface. We reasoned that it might be possible to prepare probe-carrying somatostatin analogues that would escape recycling, efficiently depositing probe molecules inside cells and ultimately increasing their intracellular concentration. We have incorporated cathepsin-B-cleavable linkers into (Tyr3)-octreotate chelate conjugates and examined these constructs as to cellular uptake, externalization, subcellular localization, and cleavage in the rat pancreatic tumor cell line AR42J in culture. Comparison of the cleavable radioligands with a noncleavable control indicates that scission of the constituent cathepsin B substrate occurs at a rate faster than ligand externalization, depositing virtually all internalized cleaved radiochelates within lysosomal compartments.
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PMID:Evaluation of cleavable (Tyr3)-octreotate derivatives for longer intracellular probe residence. 1514 93

This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis.
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PMID:New advances in cell physiology and pathophysiology of the exocrine pancreas. 2152 56

To improve cancer selectivity of imaging agents, we synthesized the triple-targeting, near-infrared (NIR) based fluorogenic probe, Oct-FK(PBA)-NIR. The new probe consists of (1) octreotide as a synthetic ligand of somatostatin receptors, (2) a H2O2-responsive phenylboronic acid, (3) a dipeptide substrate for cathepsin B, and (4) a NIR fluorophore. The results of cell studies show that the probe can be used for selective imaging of cancer cells in the NIR range without interference with normal cells.
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PMID:Preparation of a Multiple-Targeting NIR-Based Fluorogenic Probe and Its Application for Selective Cancer Cell Imaging. 3118 88