In pancreatic β-cells, glutamate has been proposed to mediate insulin secretion as a glucose-derived factor, although it is also considered for its sole catabolic function. Hence, changes in cellular ...glutamate levels are a matter of debate. Here, we investigated the effects of glucose and the glutamate precursor glutamine on kinetics of glutamate levels together with insulin secretion in INS-1E β-cells. Preincubation at low (1 mM) glucose resulted in reduced cellular glutamate levels, which were doubled by exposure to glutamine. In glutamine-deprived cells, 5 mM glucose restored glutamate concentrations. Incubation at 15 mM glucose increased cellular glutamate, along with stimulation of insulin secretion, following both glutamine-free and glutamine-rich preincubations. Nuclear magnetic resonance (NMR) spectroscopy of INS-1E cells exposed to 15 mM
D-1-
13Cglucose revealed glutamate as the major glucose metabolic product. Branched-chain amino acids, such as leucine, reduced cellular glutamate levels at low and intermediate glucose. This study demonstrates that glucose stimulates glutamate generation, whereas branched-chain amino acids promote competitive glutamate expenditure.
Among the phase diagrams of six binary systems composed of alkali metals, Sodium (Na), Potassium (K), Rubidium (Rb) and Cesium (Cs), three of them, those of the Cs–K, Cs–Rb and K–Rb systems, indicate ...a complete range of solid solubility, and the other three, those of the Cs–Na, K–Na and Na–Rb systems, have the eutectic type characteristic. The computational thermodynamic descriptions of the six binary systems were modeled by the CALPHAD technique. The solution phases, liquid and body-centered cubic, were described using a substitution model, with the excess Gibbs energies formulated by the Redlich–Kister expression. The intermediate phases with no solubility ranges, KNa
2 and CsNa
2, were treated as stoichiometric compounds. The thermodynamic properties and the phase diagrams of the six binary systems were predicted. The consistency between the calculated results and the reported experimental measurements for the phase equilibria and the thermochemical properties has been obtained for all of the six binary systems.
► Six binary systems (Cs–K, Cs–Na, Cs–Rb, K–Na, K–Rb, Na–Rb) were optimized. ► A self-consistent set of thermodynamic parameters was obtained. ► Experimental thermodynamic and phase equilibrium data were well reproduced.
The study addressed the functional link between remodelling of the actomyosin cytoskeleton in pancreatic β‐cells and the regulation of insulin secretion. Confocal microscopy revealed that myosin ...heavy chain (MHC) IIA co‐localized very well with filamentous (F)‐actin in RINm5F cells but MHCIIB did not. Subcellular localization of MHCIIB was not altered by stimulation with 30 mM KCl (which evokes Ca2+‐dependent insulin secretion). In contrast MHCIIA redistributed in a manner similar to F‐actin, especially towards the apical surface, but also away from peripheral regions towards cell contact points on the basal surface. Finally, Ca2+‐dependent insulin secretion was inhibited by stabilization of actin filaments with jasplakinolide. The results support a role for the MHCIIA/actin cytoskeleton in regulating insulin secretion.
Metabolism of Dopamine by the Nasal Mucosa Chemuturi, Nagendra V.; Donovan, Maureen D.
Journal of pharmaceutical sciences,
November 2006, Letnik:
95, Številka:
11
Journal Article
Recenzirano
The nasal route of administration offers several advantages over oral and intravenous administration, including the ability to avoid hepatic first pass metabolism. Dopamine deficiency has been ...associated with several neurological disorders; it has been shown to have good systemic bioavailability and significant uptake into the CNS following intranasal administration. The purpose of these studies was to investigate the limiting role of mucosal metabolism of dopamine during nasal absorption. In vitro transport and initial rate studies were carried out using nasal mucosal explants to study dopamine permeability and metabolism. Dihydroxyphenylacetic acid (DOPAC) was the only metabolite detected. Monoamine oxidase (MAO), the enzyme responsible for DOPAC formation, was localized to the submucosal region of the nasal explants. The amount of DOPAC formed during the transport studies was less than 0.5% of the initial amount of dopamine placed into the system. Iproniazid, an MAO inhibitor, blocked DOPAC formation but had no effect on dopamine transport. The limited extent of dopamine metabolism compared to its mucosal transport demonstrates that nasal dopamine transport is not significantly reduced by mucosal metabolism and suggests that the nasal route may be promising for the efficient delivery of dopamine to the CNS.
The putative Rab3 effector RIM (Rab3-interacting molecule) was detected by Northern blotting, RT-PCR and Western blotting in native pancreatic β-cells as well as in the derived cell lines INS-1E and ...HIT-T15. RIM was localized on the plasma membrane of INS-1E cells and β-cells. An involvement of RIM in insulin exocytosis was indicated by transfection experiments of INS-1E cells with the Rab3 binding domain of RIM. This domain enhanced glucose-stimulated secretion in intact cells and Ca
2+-stimulated exocytosis in permeabilized cells. Co-expression of Rab3A reversed the effect of RIM on exocytosis. These results suggest an implication of RIM in the control of insulin secretion.
There is growing evidence that nitric oxide serves as a neurotransmitter released from enteric inhibitory nerves in the gastrointestinal tract. The distribution of nitric oxide synthase suggests that ...nitric oxide may also be a neurotransmitter within enteric ganglia. Since many actions of nitric oxide are mediated by stimulation of soluble guanylate cyclase and a subsequent increase in 3',5'-cyclic guanosine monophosphate (cGMP) concentration, targets for nitric oxide in the canine proximal colon were investigated by immunohistochemical localization of cGMP. In the presence of phosphodiesterase inhibitors (M&B 22948, 100 microM and 3-isobutyl-1-methyl-xanthine, 1 mM), exogenous nitric oxide and electrical field stimulation caused an accumulation of cGMP-like immunoreactivity in several cell-types including colonic smooth muscle cells. cGMP-like immunoreactivity was also observed in a subpopulation of neurons in both myenteric and submucosal ganglia. Sequential labeling with the NADPH diaphorase technique showed that 94% of neurons that responded to exogenous nitric oxide with an increase in cGMP-like immunoreactivity were NADPH diaphorase negative. None of the myenteric neurons that responded to electrical field stimulation with an increase in cGMP-like immunoreactivity were NADPH diaphorase positive, and only one submucosal neuron with cGMP-like immunoreactivity was also NADPH diaphorase positive. The electrical field-stimulated increase in cGMP-like immunoreactivity was blocked by nitroarginine (100 microM). An increase in cGMP-like immunoreactivity also occurred in interstitial cells located at the submucosal surface of the circular muscle layer. These cells are interposed between nerve varicosities and smooth muscle cells and may partially mediate neuromuscular transmission. Sodium nitroprusside and nitric oxide also caused an accumulation of cGMP-like immunoreactivity in smooth muscle cells of intramural arterioles and venules. The results of this study further support the role of nitric oxide as a neurotransmitter in colonic muscles, and provide support for the hypothesis that interstitial cells are functionally innervated by enteric inhibitory neurons. The data also suggest that nitric oxide may serve as a neurotransmitter in enteric ganglia.
The KRb (2)3Σ+ Electronic State Amiot, C.
Journal of molecular spectroscopy,
September 2000, 2000-09-00, Letnik:
203, Številka:
1
Journal Article
Recenzirano
High-resolution spectra of the (3)1Π → (2)3Σ+ system of the KRb molecule, obtained after excitation with fixed frequencies Ar+ laser lines, were recorded on a Connes-type Fourier transform ...interferometer. Molecular constants of the first 14 vibrational levels of the (2)3Σ+ state are determined. The RKR potential energy curve is derived. The main spectroscopic constants for this triplet electronic state of the 39K 85Rb isotopic species are Te = 13 507.146(2) cm−1, ωe = 48.6385(6) cm−1, Be = 0.0254152(5) cm−1, γ = 0.00164(4) cm−1, ϵ = −0.469(2) cm−1, Re = 4.98345 Å, De = 3447 cm−1.
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