Glucagon-like peptide-1 induces a cAMP-dependent increase of [Na+]i associated with insulin secretion in pancreatic β-cells

2003 ◽  
Vol 285 (5) ◽  
pp. E1001-E1009 ◽  
Author(s):  
Yoshikazu Miura ◽  
Hisao Matsui
Keyword(s):  
Insulin Secretion ◽  
Adenylate Cyclase ◽  
Islet Cells ◽  
Free Calcium ◽  
Dependent Manner ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) elevates the intracellular free calcium concentration ([Ca2+]i) and insulin secretion in a Na+-dependent manner. To investigate a possible role of Na ion in the action of GLP-1 on pancreatic islet cells, we measured the glucose-and GLP-1-induced intracellular Na+ concentration ([Na+]i), [Ca2+]i, and insulin secretion in hamster islet cells in various concentrations of Na+. The [Na+]i and [Ca2+]i were monitored in islet cells loaded with sodium-binding benzofuran isophthalate and fura 2, respectively. In the presence of 135 mM Na+ and 8 mM glucose, GLP-1 (10 nM) strongly increased the [Na+]i, [Ca2+]i, and insulin secretion. In the presence of 13.5 mM Na+, both glucose and GLP-1 increased neither the [Na+]i nor the [Ca2+]i. In a Na+-free medium, GLP-1 and glucose did not increase the [Na+]i. SQ-22536, an inhibitor of adenylate cyclase, and H-89, an inhibitor of PKA, incompletely inhibited the response. In the presence of both 8 mM glucose and H-89, 8-pCPT-2′-O-Me-cAMP, a PKA-independent cAMP analog, increased the insulin secretion and the [Na+]i. Therefore, we conclude that GLP-1 increases the cAMP level via activation of adenylate cyclase, which augments the membrane Na+ permeability through PKA-dependent and PKA-independent mechanisms, thereby increasing the [Ca2+]i and promoting insulin secretion from hamster islet cells.

P2 purinoceptor localization along rat nephron and evidence suggesting existence of subtypes P2Y1 and P2Y2

1998 ◽  
Vol 274 (6) ◽  
pp. F1006-F1014 ◽  
Author(s):  
Seok Ho Cha ◽  
Takashi Sekine ◽  
Hitoshi Endou
Keyword(s):  
Calcium Concentration ◽  
Free Calcium ◽  
Dependent Manner ◽  
Reactive Blue 2 ◽  
Collecting Tubule ◽  
Single Nephron ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration ◽  
Dose Dependent ◽  
Cortical Collecting Tubule

Effects of extracellular ATP on intracellular free calcium concentration ([Ca2+]i) were examined in rat single nephron segments using the fura 2-AM. ATP (10 μM) induced a significant transient increase in [Ca2+]iin the glomerulus, the early proximal convoluted tubule (S1), the cortical collecting tubule (CCT), and the outer medullary collecting tubule (OMCT). The magnitude of the response was the greatest in the OMCT among four segments. ATP induced an increase in the [Ca2+]iin a dose-dependent manner in S1 and OMCT. In the OMCT, ATP caused a biphasic increase in [Ca2+]iconsisting of an initial rapid rise and a sustained phase. Removal of calcium from the medium resulted in an attenuation of the sustained phase of [Ca2+]iand an ∼30% reduction in the height of the initial [Ca2+]ipeak in response to 10 μM ATP. Effects of ATP, its analogs, and its metabolites were tested in the S1 and OMCT. ATP, 2-methylthio-ATP (2-MeS-ATP), ADP, and UTP increased [Ca2+]idose dependently. AMP and adenosine did not affect [Ca2+]iin the S1 and OMCT. The ATP- or 2-MeS-ATP-induced [Ca2+]iincrease was inhibited by the pretreatment of the S1 and OMCT with suramin or reactive blue 2. Neomycin, a phospholipase C inhibitor, attenuated the ATP-induced [Ca2+]iincrease. To investigate the hormonelike action of ATP in OMCT, a heterologous cross desensitization was performed. The pretreatment of OMCT with ATP inhibited increases in vasopressin-, ANG II-, endothelin-1-, or bradykinin-induced [Ca2+]iincrease. These findings suggest that ATP might affect the above peptidyl agonist-activated calcium mobilizations.

Cholinergic effects on intracellular free calcium concentration in renal corpuscle: role of parietal sheet

1992 ◽  
Vol 262 (2) ◽  
pp. F248-F255
Author(s):  
F. Lebrun ◽  
F. Morel ◽  
G. Vassent ◽  
J. Marchetti
Keyword(s):  
Calcium Release ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Response Curves ◽  
Glomerular Function ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration ◽  
External Calcium ◽  
Cholinergic Effects

To investigate a possible effect of cholinergic agonists on the renal glomerular function, fura-2 microfluorometric measurements of intracellular free calcium [( Ca2+]i) were performed on single intact glomeruli, single isolated parietal sheets of the Bowman's capsule and single parietal sheet-deprived glomeruli (PS-D glomerulus). Carbachol (10(-4) M), in the presence of 2 mM external calcium, induced a biphasic increase in [Ca2+]i characterized by a sharp initial peak followed by a sustained plateau in the whole glomerulus (delta [Ca2+]i = 177 +/- 13 and 70 +/- 7 nM, respectively; n = 21) and in the parietal sheet (418 +/- 30 and 111 +/- 13 nM, respectively; n = 21). In the PS-D glomerulus (n = 9), the response was less marked and included a barely visible peak (77 +/- 13 nM) and a relatively low plateau (49 +/- 11 nM). In the absence of external calcium, the peak phase was preserved in the three structures, indicating a calcium release from intracellular pools, whereas the plateau, due to the entry of external calcium, was suppressed. These effects were fully inhibited by 10(-4) M of either atropine or pirenzepine, demonstrating the muscarinic nature of the receptors. Dose-response curves showed that the parietal sheet was more sensitive to the physiological agonist (acetylcholine) than to carbachol. A still unexplained difference in sensitivity was noted between peak and plateau, respectively (half-maximal responses were 5 x 10(-6) vs. 5 x 10(-7) M for carbachol and 2 x 10(-7) vs. 3 x 10(-8) M for acetylcholine).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ingestion of coffee polyphenols increases postprandial release of the active glucagon-like peptide-1 (GLP-1(7–36)) amide in C57BL/6J mice

2015 ◽  
Vol 4 ◽  
Author(s):  
Yoshie Fujii ◽  
Noriko Osaki ◽  
Tadashi Hase ◽  
Akira Shimotoyodome
Keyword(s):  
Insulin Secretion ◽  
Human Subjects ◽  
Coffee Consumption ◽  
Epidemiological Studies ◽  
Diabetes Risk ◽  
Dependent Manner ◽  
Diabetes In Animals ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dose Dependent

AbstractThe widespread prevalence of diabetes, caused by impaired insulin secretion and insulin resistance, is now a worldwide health problem. Glucagon-like peptide 1 (GLP-1) is a major intestinal hormone that stimulates glucose-induced insulin secretion from β cells. Prolonged activation of the GLP-1 signal has been shown to attenuate diabetes in animals and human subjects. Therefore, GLP-1 secretagogues are attractive targets for the treatment of diabetes. Recent epidemiological studies have reported that an increase in daily coffee consumption lowers diabetes risk. The present study examined the hypothesis that the reduction in diabetes risk associated with coffee consumption may be mediated by the stimulation of GLP-1 release by coffee polyphenol extract (CPE). GLP-1 secretion by human enteroendocrine NCI-H716 cells was augmented in a dose-dependent manner by the addition of CPE, and was compatible with the increase in observed active GLP-1(7–36) amide levels in the portal blood after administration with CPE alone in mice. CPE increased intracellular cyclic AMP (cAMP) levels in a dose-dependent manner, but this was not mediated by G protein-coupled receptor 119 (GPR119). The oral administration of CPE increased diet (starch and glyceryl trioleate)-induced active GLP-1 secretion and decreased glucose-dependent insulinotropic polypeptide release. Although CPE administration did not affect diet-induced insulin secretion, it decreased postprandial hyperglycaemia, which indicates that higher GLP-1 levels after the ingestion of CPE may improve insulin sensitivity. We conclude that dietary coffee polyphenols augment gut-derived active GLP-1 secretion via the cAMP-dependent pathway, which may contribute to the reduced risk of type 2 diabetes associated with daily coffee consumption.

scholarly journals Sphingosine 1-Phosphate Mobilizes Sequestered Calcium, Activates Calcium Entry, and Stimulates Deoxyribonucleic Acid Synthesis in Thyroid FRTL-5 Cells*

Endocrinology ◽  
1997 ◽  
Vol 138 (10) ◽  
pp. 4049-4057 ◽  
Author(s):  
Kid Törnquist ◽  
Pia Saarinen ◽  
Minna Vainio ◽  
Mikael Ahlström
Keyword(s):  
Tyrosine Kinases ◽  
Cell Types ◽  
Acid Synthesis ◽  
Calcium Entry ◽  
Free Calcium ◽  
Dependent Manner ◽  
Deoxyribonucleic Acid Synthesis ◽  
Sphingosine 1 Phosphate ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration

Abstract Sphingosine 1-phosphate (SPP) potently mobilizes sequestered calcium and is a mitogen in several cell types. In the present investigation, we have evaluated the effect of SPP on intracellular free calcium concentration ([Ca2+]i) and synthesis of DNA in thyroid FRTL-5 cells. SPP rapidly and transiently mobilized sequestered calcium and stimulated entry of extracellular calcium. The entry of calcium, but not the mobilization, was in part inhibited by pretreatment with pertussis toxin (Ptx), and by activation of protein kinase C. SPP did not stimulate the production of inositol 1,4,5-trisphosphate. SPP stimulated the incorporation of 3H-thymidine in a time- and dose-dependent manner. The effect was not inhibited by Ptx. Furthermore, SPP stimulated the activation of the proto-oncogene c-fos. SPP rapidly tyrosine-phosphorylated an approximately 66 kDa protein. This phosphorylation persisted for at least 1 h. Pretreatment of the cells with genistein abolished the SPP-evoked tyrosine phosphorylation, and attenuated the SPP-evoked increase in[ Ca2+]i. Furthermore, the SPP-evoked activation of Na+-H+ exchange was inhibited by genistein. The phosphorylation was not attenuated by pretreatment of the cells with Ptx. SPP per se did not affect cellular cAMP levels but attenuated the TSH-evoked increase in cAMP. As the effect of SPP might be due to activation of phospholipase D, we tested whether phosphatidic acid (PA) mobilized calcium or stimulated the incorporation of 3H-thymidine. PA mobilized sequestered calcium but did not stimulate calcium entry. PA very modestly enhanced the incorporation of 3H-thymidine. Our results suggest, that SPP stimulates DNA synthesis and activates entry of calcium in FRTL-5 cells. The effect on calcium entry appears to be dependent, at least in part, on one or several tyrosine kinases.

Regulation of energy liberation during steady sarcomere shortening

2005 ◽  
Vol 289 (5) ◽  
pp. H2176-H2182 ◽  
Author(s):  
Oren Tchaicheeyan ◽  
Amir Landesberg
Keyword(s):  
Energy Liberation ◽  
Free Calcium ◽  
Relative Role ◽  
Shortening Velocity ◽  
Velocity Relationship ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration ◽  
Strong Transition ◽  
Force Velocity

Energy liberation rate ( Ė) during steady muscle shortening is a monotonic increasing or biphasic function of the shortening velocity ( V). The study examines three plausible hypotheses for explaining the biphasic Ė-V relationship (EVR): 1) the cross-bridge (XB) turnover rate from non-force-generating (weak) to force-generating (strong) conformation decreases as V increases; 2) XB kinetics is determined by the number of strong XBs (XB -XB cooperativity); and 3) the affinity of troponin for calcium is modulated by the number of strong XBs (XB -Ca cooperativity). The relative role of the various energy-regulating mechanisms is not well defined. The hypotheses were tested by coupling calcium kinetics with XB cycling. All three hypotheses yield identical steady-state characteristics: 1) hyperbolic force-velocity relationship; 2) quasi-linear stiffness-force relationship; and 3) biphasic EVR, where Ė declines at high V due to decrease in the number of cycling XBs or in the weak-to-strong transition rate. The hypotheses differ in the ability to describe the existence of both monotonic and biphasic EVRs and in the effect of intracellular free calcium concentration ([Ca2+]i) on the EVR peak. Monotonic and biphasic EVRs with a shift in EVR peak to higher velocity at higher [Ca2+]i are obtained only by XB -Ca cooperativity. XB -XB cooperativity provides only biphasic EVRs. A direct effect of V on XB kinetics predicts that EVR peak is obtained at the same velocity independently of [Ca2+]i. The study predicts that measuring the dependence of the EVR on [Ca2+]i allows us to test the hypotheses and to identify the dominant energy-regulating mechanism. The established XB -XB and XB -Ca mechanisms provide alternative explanations to the various reported EVRs.

scholarly journals TNF signaling impacts glucagon-like peptide-1 expression and secretion

2018 ◽  
Vol 61 (4) ◽  
pp. 153-161 ◽  
Author(s):  
Sufang Chen ◽  
Wei Wei ◽  
Minjie Chen ◽  
Xiaobo Qin ◽  
Lianglin Qiu ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Deficient Mice

Numerous studies have implicated tumor necrosis factor α (TNFα) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNFα, lymphotoxin α (LTα) binds to and activates TNFR1. Thus, TNFα and LTα together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1−/−), TNFα/LTα/LTβ triple-deficient mice (TNF/LT∆3) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1−/− and TNF/LT∆3 mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.

scholarly journals Actions of glucagon-like peptide-1 on KATP channel-dependent and -independent effects of glucose, sulphonylureas and nateglinide

2006 ◽  
Vol 190 (3) ◽  
pp. 889-896 ◽  
Author(s):  
Neville H McClenaghan ◽  
Peter R Flatt ◽  
Andrew J Ball
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Channel Dependent ◽  
Releasing Effect ◽  
Independent Effects

This study examined the effects of glucagon-like peptide-1 (GLP-1) on insulin secretion alone and in combination with sulphonylureas or nateglinide, with particular attention to KATP channel-independent insulin secretion. In depolarised cells, GLP-1 significantly augmented glucose-induced KATP channel-independent insulin secretion in a glucose concentration-dependent manner. GLP-1 similarly augmented the KATP channel-independent insulin-releasing effects of tolbutamide, glibenclamide or nateglinide. Downregulation of protein kinase A (PKA)- or protein kinase C (PKC)-signalling pathways in culture revealed that the KATP channel-independent effects of sulphonylureas or nateglinide were critically dependent upon intact PKA and PKC signalling. In contrast, GLP-1 exhibited a reduced but still significant insulin-releasing effect following PKA and PKC downregulation, indicating that GLP-1 can modulate KATP channel-independent insulin secretion by protein kinase-dependent and -independent mechanisms. The synergistic insulin-releasing effects of combinatorial GLP-1 and sulphonylurea/nateglinide were lost following PKA- or PKC-desensitisation, despite GLP-1 retaining an insulin-releasing effect, demonstrating that GLP-1 can induce insulin release under conditions where sulphonylureas and nateglinide are no longer effective. Our results provide new insights into the mechanisms of action of GLP-1, and further highlight the promise of GLP-1 or similarly acting analogues alone or in combination with sulphonylureas or meglitinide drugs in type 2 diabetes therapy.

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