Abstract：
:Insulin secretion in humans is usually induced by mixed meals, which upon ingestion, increase the plasma concentration of glucose, fatty acids, amino acids, and incretins like glucagon-like peptide 1. Beta-cells can stay in the off-mode, ready-mode or on-mode; the mode-switching being determined by the open state probability of the ATP-sensitive potassium channels, and the activity of enzymes like glucokinase, and glutamate dehydrogenase. Mitochondrial metabolism is critical for insulin secretion. A sound understanding of the intermediary metabolism, electrophysiology, and cell signaling is essential for comprehension of the entire spectrum of the stimulus-secretion coupling. Depolarization brought about by inhibition of the ATP sensitive potassium channel, together with the inward depolarizing currents through the transient receptor potential (TRP) channels, leads to electrical activities, opening of the voltage-gated calcium channels, and exocytosis of insulin. Calcium- and cAMP-signaling elicited by depolarization, and activation of G-protein-coupled receptors, including the free fatty acid receptors, are intricately connected in the form of networks at different levels. Activation of the glucagon-like peptide 1 receptor augments insulin secretion by amplifying calcium signals by calcium induced calcium release (CICR). In the treatment of type 2 diabetes, use of the sulfonylureas that act on the ATP sensitive potassium channel, damages the beta cells, which eventually fail; these drugs do not improve the cardiovascular outcomes. In contrast, drugs acting through the glucagon-like peptide-1 receptor protect the beta-cells, and improve cardiovascular outcomes. The use of the glucagon-like peptide 1 receptor agonists is increasing and that of sulfonylurea is decreasing. A better understanding of the stimulus-secretion coupling may lead to the discovery of other molecular targets for development of drugs for the prevention and treatment of type 2 diabetes.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Islam MSdoi
10.1007/978-3-030-12457-1_37subject
Has Abstractpub_date
2020-01-01 00:00:00pages
943-963eissn
0065-2598issn
2214-8019journal_volume
1131pub_type
杂志文章,评审abstract：:After the initial discovery of neuropilin-1 as an epitope on axons recognized by a monoclonal antibody, neuropilins were rediscovered in the search for receptors mediating the repulsive actions of class 3 Semaphorins, notably Sema3A. Neuropilins are the ligand binding moieties in the class 3 Semaphorin receptor comple...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：
更新日期：2002-01-01 00:00:00
abstract：:We investigated whether taurine chloramine (TauCl), which is -endogenously produced by immune cells such as macrophages that infiltrate adipose tissue, affects the differentiation of preadipocytes into adipocytes or modulates the expression of adipokines in adipocytes. To study the physiological effects of TauCl on hu...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4614-6130-2_21
更新日期：2013-01-01 00:00:00
abstract：:The process of creating a translation-competent mRNA is highly complex and involves numerous steps including transcription, splicing, addition of modifications, and, finally, export to the cytoplasm. Historically, much of the research on regulation of gene expression at the level of the mRNA has been focused on either...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-31434-7_2
更新日期：2019-01-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is one of the major forms of motor neuron disease (MND), a group of degenerative disorders causing progressive motor neuron death leading to eventual paralysis and death. The pathogenesis of MND is poorly understood and may include genetic and/or environmental factors, with a common...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：
更新日期：2008-01-01 00:00:00
abstract：:Two species of T-kininogen which release T-kinin (Ile-Ser-bradykinin) have been purified from plasma of rats treated with Freund's complete adjuvant. The molecular weight was estimated to be 69,000 for either T-kininogen I and II by SDS-polyacrylamide gel electrophoresis. Trypsin released one mole of T-kinin from one ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-5143-6_10
更新日期：1986-01-01 00:00:00
abstract：:At this point, it may be worthwhile to list, in summary form, the important aspects of divalent cation and nucleotide binding to actin that have been reviewed here: 1) High affinity divalent cation binding to actin is very tight, with equilibrium dissociation constant KCa approximately 1 nM and KMg approximately 5 nM ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4615-2578-3_4
更新日期：1994-01-01 00:00:00
abstract：:During wakefulness, cerebral blood flow (CBF) is closely coupled to regional cerebral metabolism; however CBF is also strongly modulated by breathing, increasing in response to both hypercapnia and hypoxia. During stage III/IV non-rapid eye (NREM) sleep, cerebral metabolism and CBF decrease whilst the partial pressure...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-0-387-34817-9_7
更新日期：2006-01-01 00:00:00
abstract：:The phospho-sphingolipid, ceramide 1-phosphate (C1P), has long been implicated as a dynamic bioactive agent. Over two decades of research has begun to characterize various regulatory roles for C1P from mammalian inflammatory response and wound healing to cellular proliferation and survival. As a metabolite of the intr...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-030-21162-2_5
更新日期：2019-01-01 00:00:00
abstract：:High concentrations of air pollutants are characteristic of the vicinity of urban busy roads. Numerous studies have shown that these concentrations are significantly higher in comparison with areas located in a certain distance from roads and especially those in rural areas. Inhabitants living in the proximity of road...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/5584_2014_13
更新日期：2015-01-01 00:00:00
abstract：:DNA methyltransferases (MTases) uniquely combine the ability to recognize and covalently modify specific target sequences in DNA using the ubiquitous cofactor S-adenosyl-L-methionine (AdoMet). Although DNA methylation plays important roles in biological signaling, the transferred methyl group is a poor reporter and is...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-43624-1_19
更新日期：2016-01-01 00:00:00
abstract：:In isometric contraction, a high proportion of crossbridges are always in the attached state and crossbridge cycling is slow. During shortening, crossbridges must be entering the detached state at a higher rate, as they come to the end of their working strokes. The size of the population of detached crossbridges will ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
abstract：:Laser diffraction and photomicrography have been used to monitor sarcomere length changes in single muscle fibres of the frog, at long sarcomere lengths, during fixed end tetani. In the central 90% of all fibres, changes in sarcomere length were consistently less than 0.25 micron. Sarcomere length showed an initial ra...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-4703-3_42
更新日期：1984-01-01 00:00:00
abstract：:The impulse oscillometry (IOS) is recognized as a complementary method to spirometry in the diagnostics of obstructive pulmonary disorders. The IOS enables to measure total respiratory resistance (R5) and proximal respiratory resistance (R20), with the R5-R20 difference reflecting small airway resistance. This study s...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/5584_2016_208
更新日期：2017-01-01 00:00:00
abstract：:The aim of this study was to develop a simple technique for objective assessment of mental stress levels by measuring hemoglobin concentration changes in the bilateral prefrontal cortex (PFC) at rest, employing two-channel near-infrared spectroscopy (NIRS). Each subject was instructed to think about nothing in particu...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4614-7411-1_52
更新日期：2013-01-01 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature that is characterized by vascular obstruction and progressive right ventricular failure. One hallmark of clinical PAH is its very poor survival, with PAH mortality rates approximating those of many malignancies. The discovery that the fawn...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-60761-500-2_11
更新日期：2010-01-01 00:00:00
abstract：:Initial attempts to model urinary folate reabsorption using cultures of HPT cells on porous filter inserts produced disappointing results in that large amounts of 5M were transported across the epithelial monolayer in a nonspecific manner. Since the impermeable molecule inulin was also transported, there apparently ex...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-2960-6_155
更新日期：1993-01-01 00:00:00
abstract：:The basis of the present investigation was the establishment of an oncogene-dependent, genetically determined two-stage carcinogenesis in vitro model as multicellular spheroids. Spheroid formation was achieved with four rat embryo fibroblast cell lines, two of which represent the first step of malignant transformation...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-2468-7_47
更新日期：1994-01-01 00:00:00
abstract：:A comprehensive synthetic approach was employed to identify the continuous regions of T-cell recognition on the alpha-chain of Torpedo californica acetylcholine receptor (AChR). Eighteen synthetic consecutive overlapping peptides, of uniform size and overlaps, that spanned the entire extracellular part (residues 1-210...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-5442-0_8
更新日期：1987-01-01 00:00:00
abstract：:An arginine-specific ADP-ribosyltransferase activity was detected in chicken spleen membrane fraction using a capillary electrophoresis assay and the activity was extracted by phosphatidylinositol-specific phospholipase C but not by 1 M NaCl or 1% Triton X-100. The enzyme protein was purified from chicken spleen membr...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4419-8632-0_30
更新日期：1997-01-01 00:00:00
abstract：:The first purpose of this work was to obtain direct evidence that tissue kallikreins cleave arginyl bonds when the leaving group is Arg-Val, and on the contrary, do not split them when it is Arg-Pro; the second aim was to ascertain whether this specificity could be used as a criterion, for characterizing tissue kallik...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-5143-6_33
更新日期：1986-01-01 00:00:00
abstract：:Autophagy plays a crucial role in maintaining cellular homeostasis, and is closely related to the occurrence of variety of human diseases. It is known that autophagy occurs in response to various environmental stresses such as nutrient deficiency, growth factor deficiency, and hypoxia. Induced autophagy eliminates the...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-981-15-0602-4_3
更新日期：2019-01-01 00:00:00
abstract：:Spinal and Bulbar Muscular Atrophy (SBMA) is an inherited neuromuscular disorder caused by a CAG-polyglutamine (polyQ) repeat expansion in the androgen receptor (AR) gene. Unlike other polyQ diseases, where the function of the native causative protein is unknown, the biology of AR is well understood, and this knowledg...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-71779-1_5
更新日期：2018-01-01 00:00:00
abstract：:Alcohol drinking increases the risk for a number of cancers. Currently, the highest risk (Group 1) concerns oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, as assessed by the International Agency for Research on Cancer (IARC). Alcohol and other beverage constituents, their metabolic effe...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-09614-8_3
更新日期：2015-01-01 00:00:00
abstract：:Changes in tumor tissue oxygenation and acidity were determined using ultramicroelectrodes, and presented in histogram fashion. The effect of Hyperthermia and Hpd photo-therapy were tested. It was found that both modalities affect tumor microcirculation, causing a marked drop in oxygen availability. Tissue pH is decre...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-7790-0_55
更新日期：1983-01-01 00:00:00
abstract：:Kallikrein was purified from horse kidney by several steps of chromatographic procedure and by affinity chromatography on Sepharose-Concanavaline. Horse urinary kallikrein was previously purified by DE-32 hydroxylapatite and by Sephadex G-100 gel filtration. On the purified final sample of renal and urinary kallikrein...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4757-0926-1_31
更新日期：1979-01-01 00:00:00
abstract：:In the field of pathology it is clear that molecular genomics and digital imaging represent two promising future directions, and both are as relevant to the tumor microenvironment as they are to the tumor itself (Beck AH et al. Sci Transl Med 3(108):108ra113-08ra113, 2011). Digital imaging, or whole slide imaging (WSI...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-42023-3_1
更新日期：2016-01-01 00:00:00
abstract：:Surprisingly few transcription factors drive animal development relative to the number and diversity of final tissues and body structures. Therefore, most transcription factors must function in more than one tissue. In a famous example, members of the Hox transcription factor family are expressed in contiguous stripes...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4614-0659-4_6
更新日期：2012-01-01 00:00:00
abstract：:It is now well established that carotid bodies are sensory organs for monitoring arterial blood oxygen levels and trigger reflexes that are critical for maintaining homeostasis during hypoxemia. This review article provides a brief account of the early studies leading to the discovery of the carotid body as a sensory ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-55231-6_1
更新日期：2017-01-01 00:00:00
abstract：:The possible molecular conformations of four structurally and biologically different lipoxins derivatives were predicted by a systematic structure tree theoretical analysis. This method takes into account the London-Van der Waals energy of interaction, the electrostatic interaction, the rotation energy of the torsiona...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4757-0937-7_8
更新日期：1988-01-01 00:00:00
abstract：:The gene coding for the surface spike protein gp195 of TGEV has been cloned and expressed in E. coli in the form of fusion proteins. These proteins were isolated and used to immunize laboratory animals. All animals developed antibodies cross-reacting with the TGEV virion but failed to neutralize the virus. The entire ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-7974-4_4
更新日期：1985-01-01 00:00:00
