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Associated Methods
Published in Lars-Inge Larsson, Immunocytochemistry: Theory and Practice, 2020
Hence, these data clearly show that some intracellular proteins destined for export by the regulated pathway (exocytosis), or being integral secretory granule constituents, appear on the cell surface during stimulation and may be amenable to interaction with specific antibodies.
The Endocrine Pancreas
Published in George H. Gass, Harold M. Kaplan, Handbook of Endocrinology, 2020
Other protein constituents of the secretory granule besides insulin, C-peptide, and processing enzymes include p-granin (a conversion product of chromogrannin A), pancreastatin, and islet amyloid polypeptide (IAPP). The biologic function of these molecules is uncertain, although intense interest surrounds their potential roles in the pathophysiology of diabetes. Whereas no function of isolated C-peptide other than in the folding of the proinsulin molecule could be demonstrated in initial studies, recent interest has turned to the potential role of the absence of C-peptide in the development of complications of insulin-dependent diabetes and in the development of insulin resistance.8 Pancreastatin reportedly inhibits insulin release.9 IAPP is found in insoluble amyloid deposits within islets in non—insulin-dependent diabetes mellitus (NIDDM) as well as within insulinomas. Some have postulated that IAPP may play a role in the insulin secretory defect and/or peripheral insulin resistance observed in diabetes, but compelling evidence for both is lacking.10
Pathophysiology and Clinical Management of Diabetes and Prediabetes
Published in Jeffrey I. Mechanick, Elise M. Brett, Nutritional Strategies for the Diabetic & Prediabetic Patient, 2006
Elliot J. Rayfield, Marilyn V. Valentine
Sulfonylureas (SU) are the oldest class of treatment for T2DM. The mode of action is by stimulating β-cell insulin secretion (see Figure 2.6). The β-cell SU receptor (SUR) is functionally linked to an ATP-sensitive K+ channel (K+ATP) on the cell membrane [104]. In the basal state, the K+ATP channel shifts K+ from the inside of the β-cell to the extracellular space and maintains the resting potential of the β-cell membrane. When the SU binds to the SUR, K+ efflux diminishes and the membrane depolarizes. This depolarization opens a voltage-dependent calcium channel in the same membrane which enables extracellular calcium to enter the cell. The resultant increase in intracellular calcium triggers insulin-containing secretory granule exocytosis.
The complementary roles of VAMP-2, -3, and -7 in platelet secretion and function
Published in Platelets, 2023
Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart
Compensating roles for VAMPs in granule secretion have been studied in other systems. Zhao et al. showed that V2, V3, and V8 have a major role in GLUT4 trafficking in adipocytes, but V7 does not.26 In chromaffin cells, V2 is the dominant isoform for catecholamine secretion and in its absence, V3 can efficiently compensate.27 In mast cells, the cargoes are packed into distinct subsets of secretory granules, and the release of at least some of these granules is mediated by V8, while V2 and V3 appear not to be important.28 The release of granule cargo from neutrophils is mediated by the SNARE complexes consisting of different VAMPs.29 While V2 mediated release of cargo from tertiary granules, V7 played a role in azurophilic granule release. V1 was found to be crucial for both of these release events. These studies underline the heterogeneous nature of VAMP usage in the secretory granule release from different cell types. Whether this is due to the promiscuous pairing of SNAREs to mediate membrane fusion or represents a pathway to fine-tune release kinetics in a context-specific manner remains to be determined.
Analysis of single-cell sequencing results of an elderly patient with myeloid leukemia reveals high expression of multiple oncogenes in monocytes and hematopoietic stem cells
Published in Hematology, 2023
Xiaoli Xu, Minjian Xiong, Haiyan Ye, Yonglei Qi, Ying Zhao
In order to uncover the common functions and related pathways of a large number of genes in the DEG set of monocytes compared peripheral blood with bone marrow, we performed the enrichment analysis subsequently (Figure 4(A–D)). Results of GO showed that the pathways correlated with biological process were SRP-dependent co-translational protein targeting to membrane, neutrophil activation involved in immune response, translational initiation, neutrophil activation, and neutrophil degranulation. The pathways correlated with cellular components were cytosolic ribosome, secretory granule lumen, vesicle lumen, vacuolar lumen, and primary lysosome. The pathways correlated with molecular functions were structural constituent of ribosome, DNA replication origin binding, RAGE receptor binding, single-stranded DNA binding, and protease binding. These may indicate that the patient’s monocytes continue to develop after migration to the peripheral blood from the bone marrow, and participated in the immune response and immune disorder process, and the cells’ own metabolism and function are vigorous. Further analysis showed that the above-mentioned key signaling pathways were associated or interacted with multiple genes/molecules (Figure 5(A–C)).
Identification of T cell-related biomarkers for breast cancer based on weighted gene co-expression network analysis
Published in Journal of Chemotherapy, 2023
The 296 genes in green module were subjected to enrichment analysis. GO enrichment analysis denoted that most of genes in this module were associated with biological processes including positive regulation of cytokine production, defense response to virus, and type I interferon signalling pathway. In terms of cellular component, genes were enriched in secretory granule membrane, cytoplasmic vesicle lumen, and lysosomal lumen. Regarding molecular function, the enrichments of genes were mainly GTPase activity, immune receptor activity, cytokine receptor activity, and chemokine activity (Figure 2(A)). KEGG analysis displayed that genes were mainly enriched in the signalling pathways like cytokine–cytokine receptor interaction, chemokine signalling pathway, viral protein interaction with cytokine and cytokine receptor, complement and coagulation cascades, and antigen processing and presentation (Figure 2(B)). These results unveiled that genes in green module were enriched in immune-related signalling pathways or biological processes, and green module was related to immunity.