scholarly journals A TRPM4 Inhibitor 9-Phenanthrol Inhibits Glucose- and Glucagon-Like Peptide 1-Induced Insulin Secretion from Rat Islets of Langerhans

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Zuheng Ma ◽  
Anneli Björklund ◽  
Md. Shahidul Islam
Keyword(s):  
Insulin Secretion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Monovalent Cation ◽  
Major Effect ◽  
Hyperinsulinemic Hypoglycemia ◽  
Rat Islets ◽  
Glucagon Like Peptide 1 ◽  
Transient Receptor ◽  
Rat Islets Of Langerhans

Pancreatic β-cells express several ion channels of the transient receptor potential family, which play important roles in mediating the stimulus-secretion coupling. One of these channels, the TRPM4 is a Ca2+-activated monovalent cation channel. This channel is inhibited by 9-phenanthrol, which also inhibits the TMEM16a Cl− channel, and activates the Ca2+-activated K+ channel, Kca3.1. The net effects of ion-channel modulation by 9-phenantherol on the insulin secretion remain unclear. We tested the effects of 9-phenanthrol on glucose- and GLP-1-induced insulin secretion from isolated rat islets in static incubations. When applied to the islets in the presence of 3.3 mM glucose, 9-phenanthrol caused a small increase in insulin secretion (~7% of the insulin secretion stimulated by 10 mM glucose). 10 μM 9-phenanthrol did not inhibit glucose- or GLP-1-induced insulin secretion. 20 μM and 30 μM 9-phenanthrol inhibited glucose-induced insulin secretion by ~80% and ~85%, respectively. Inhibition of the GLP-1-induced insulin secretion by 20 μM and 30 μM 9-phenanthrol was 65% and 94%, respectively. Our study shows that the major effect of 9-phenanthrol on the islets is a strong inhibition of insulin secretion, and we speculate that compounds related to 9-phenanthrol may be potentially useful in treating the pancreatogenous hyperinsulinemic hypoglycemia syndromes.

TRPC1, TRPC3, and TRPC4 in Rat Orofacial Structures

2017 ◽  
Vol 204 (5-6) ◽  
pp. 293-303 ◽  
Author(s):  
Masatoshi Fujita ◽  
Tadasu Sato ◽  
Takehiro Yajima ◽  
Eiji Masaki ◽  
Hiroyuki Ichikawa
Keyword(s):  
Transient Receptor Potential ◽  
Sympathetic Neurons ◽  
Receptor Potential ◽  
Monovalent Cation ◽  
Calcitonin Gene ◽  
Cervical Ganglion ◽  
Parasympathetic Neurons ◽  
Transient Receptor ◽  
And Function ◽  
And Control

TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide. In the superior cervical ganglion, all sympathetic neurons showed TRPC1 and TRPC3 immunoreactivity. Parasympathetic neurons in the submandibular ganglion, tongue, and parotid gland were TRPC1, TRPC3, and TRPC4 IR. Gustatory and olfactory cells were also IR for TRPC1, TRPC3, and/or TRPC4. In the musculature, motor endplates expressed TRPC1 and TRPC4 immunoreactivity. It is likely that TRPCs are associated with sensory, autonomic, and motor functions in oral and craniofacial structures.

scholarly journals The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Iordan Iordanov ◽  
Csaba Mihályi ◽  
Balázs Tóth ◽  
László Csanády
Keyword(s):  
Cell Death ◽  
Insulin Secretion ◽  
Transient Receptor Potential ◽  
Channel Gating ◽  
Receptor Potential ◽  
Cation Channel ◽  
Chimeric Proteins ◽  
Transient Receptor Potential Melastatin ◽  
Biochemical Studies ◽  
Transient Receptor

Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca2+-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 is activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous to the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported ADPR hydrolysis classified TRPM2 as a channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed a soluble NUDT9H model using chimeric proteins built from complementary polypeptide fragments of NUDT9H and NUDT9. When expressed in E.coli, chimeras containing up to ~90% NUDT9H sequence remained soluble and were affinity-purified. In ADPRase assays the conserved Nudix-box sequence of NUDT9 proved essential for activity (kcat~4-9s-1), that of NUDT9H did not support catalysis. Replacing NUDT9H in full-length TRPM2 with soluble chimeras retained ADPR-dependent channel gating (K1/2~1-5 μM), confirming functionality of chimeric domains. Thus, TRPM2 is not a 'chanzyme'. Chimeras provide convenient soluble NUDT9H models for structural/biochemical studies.

scholarly journals Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 685 ◽  
Author(s):  
Md. Shahidul Islam
Keyword(s):  
Insulin Secretion ◽  
Electrical Activity ◽  
Islets Of Langerhans ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Β Cells ◽  
Transient Receptor ◽  
Insulinoma Cells

Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

Glucagon-like peptide-1 stimulates insulin secretion by a Ca2+-independent mechanism in Zucker diabetic fatty rat islets of Langerhans

Metabolism ◽  
2000 ◽  
Vol 49 (12) ◽  
pp. 1579-1587 ◽  
Author(s):  
Seamus K. Sreenan ◽  
Anshu A. Mittal ◽  
Flora Dralyuk ◽  
William L. Pugh ◽  
Kenneth S. Polonsky ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Zucker Diabetic Fatty Rat ◽  
Rat Islets ◽  
Independent Mechanism ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Rat Islets Of Langerhans

scholarly journals TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?

2019 ◽  
Vol 7 (8) ◽  
pp. 82 ◽  
Author(s):  
Dorte X. Gram ◽  
Josefine Fribo ◽  
Istvan Nagy ◽  
Carsten Gotfredsen ◽  
Ana Charrua ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oral Glucose ◽  
Transient Receptor Potential Vanilloid ◽  
Low Grade ◽  
Oral Glucose Tolerance ◽  
Transient Receptor ◽  
Low Grade Inflammation

With a global prevalence among adults over 18 years of age approaching 9%, Type 2 diabetes mellitus (T2DM) has reached pandemic proportions and represents a major unmet medical need. To date, no disease modifying treatment is available for T2DM patients. Accumulating evidence suggest that the sensory nervous system is involved in the progression of T2DM by maintaining low-grade inflammation via the vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). In this study, we tested the hypothesis that TRPV1 is directly involved in glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1−/−) and their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, Zucker obese rats were given the small molecule TRPV1 antagonist, N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and glucose-stimulated insulin secretion was improved by both genetic inactivation (Trpv1−/− mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, the improved glucose tolerance was accompanied by a reduction in inflammatory markers in the mesenteric fat, suggesting that blockade of low-grade inflammation contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We propose that TRPV1 could be a promising therapeutic target in T2DM by improving glucose intolerance and correcting dysfunctional insulin secretion.

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