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)

Several proteins that are of importance for membrane trafficking in the nerve terminal have recently been characterized. We have used Western blot and immunohistochemistry to show that synaptotagmin, synaptobrevin/VAMP (vesicle-associated membrane protein), SNAP-25 (synaptosomal-associated protein of 25 kDa), and syntaxin proteins are present in cells of the islets of Langerhans in the endocrine pancreas. Synaptotagmin-like immunoreactivity (-LI) was localized to granules within the cytoplasm of a few endocrine cells located in the periphery of the islets, identified as somatostatin-containing cells, and in many nerve fibers within the islets. VAMP-LI was seen in granules of virtually all pancreatic islet cells and also in nerve fibers. SNAP-25-LI and syntaxin-LI were predominantly present in the plasma membrane of the endocrine cells, including insulin-producing beta cells. In situ hybridization, using isoform-specific oligonucleotide probes, detected VAMP-2, cellubrevin, SNAP-25, syntaxin 1A, 4, and 5, and munc-18 mRNAs in isolated pancreatic islets and in insulin-producing cells. The results show the presence of several synaptic proteins at protein and mRNA levels in pancreatic islet cells, suggesting that they may have specific roles in the molecular regulation of exocytosis also in insulin-secreting cells.
 ...
PMID:Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells. 780 63

Both transcription factors albumin site d-binding protein (DBP) and thyrotroph embryonic factor (TEF) are elements of the "cell-clock". Their circadian accumulation in suprachiasmatic nucleus (SCN) and peripheral tissues such as liver, kidney and lung is thought to participate in controlling circadian regulation of downstream genes. TEF and DBP control elements have never been investigated in the insulin-secreting cells, but impairment of the circadian rhythm of the beta-cells might be involved in the development of diabetic state as type 2 diabetics have lost daily temporal variations of insulin secretion. We investigated the expression pattern of TEF and DBP in insulin-secreting cells. TEF and DBP transcripts are expressed at extremely high levels in human pancreatic islets compared to other tissues, suggesting a potentially important circadian regulation of these cells. Both TEF and DPB accumulate in a circadian way in insulin-secreting cells after a serum shock known to restore circadian rhythms in cultured cells. In addition, the expression of islet-specific genes involved in glucose sensing (glucose transporter 2 (Glut2), glucokinase), insulin production (insulin) and secretion (migration inhibitory factor (MIF), somatostatin and syntaxin 1A) were modulated in the same daily rhythm as well. The circadian deregulation of these genes could therefore participate in the diabetic state development.
 ...
PMID:Circadian regulation of islet genes involved in insulin production and secretion. 1548 6

We have hypothesized that the plasma membrane protein components of the exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) complex, syntaxin 1A and SNAP-25, distinctly regulate different voltage-gated K+ (Kv) channels that are differentially distributed. Neuroendocrine islet cells (alpha, beta, delta) uniformly contain both syntaxin 1A and SNAP-25. However, using immunohistochemistry, we show that the different pancreatic islet cells contain distinct dominant Kv channels, including Kv2.1 in beta cells and Kv2.2 in alpha and delta cells, whose interactions with the SNARE proteins would, respectively regulate insulin, glucagon and somatostatin secretion. We therefore examined the regulation by syntaxin 1A and SNAP-25 of these two channels. We have shown that Kv2.1 interacts with syntaxin 1A and SNAP-25 and, based on studies in oocytes, suggested a model of two distinct modes of interaction of syntaxin 1A and the complex syntaxin 1A/SNAP-25 with the C terminus of the channel. Here, we characterized the interactions of syntaxin 1A and SNAP-25 with Kv2.2 which is highly homologous to Kv2.1, except for the C-terminus. Comparative two-electrode voltage clamp analysis in oocytes between Kv2.2 and Kv2.1 shows that Kv2.2 interacts only with syntaxin 1A and, in contrast to Kv2.1, it does not interact with the syntaxin 1A/SNAP-25 complex and hence is not sensitive to the assembly/disassembly state of the complex. The distinct regulation of these closely related channels by SNAREs may be attributed to differences in their C termini. Together with the differential distribution of these channels among islet cells, their distinct regulation suggests that the documented profound down-regulation of islet SNARE levels in diabetes could distort islet cell ion channels and secretory responses in different ways, ultimately contributing to the abnormal glucose homeostasis.
 ...
PMID:Target soluble N-ethylmaleimide-sensitive factor attachment protein receptors (t-SNAREs) differently regulate activation and inactivation gating of Kv2.2 and Kv2.1: Implications on pancreatic islet cell Kv channels. 1675 85