ACD can configure probes for the various manual and automated assays for INSULIN for RNAscope Assay, or for Basescope Assay compatible for your species of interest.
FASEB J.
2017 Jul 07
Wang Q, Pronin AN, Levay K, Almaca J, Fornoni A, Caicedo A, Slepak VZ.
PMID: 28687610 | DOI: 10.1096/fj.201700197RR
In pancreatic β cells, muscarinic cholinergic receptor M3 (M3R) stimulates glucose-induced secretion of insulin. Regulator of G protein signaling (RGS) proteins are critical modulators of GPCR activity, yet their role in β cells remains largely unknown. R7 subfamily RGS proteins are stabilized by the G protein subunit Gβ5, such that the knockout of the Gnb5 gene results in degradation of all R7 subunits. We found that Gnb5 knockout in mice or in the insulin-secreting MIN6 cell line almost completely eliminates insulinotropic activity of M3R. Moreover, overexpression of Gβ5-RGS7 strongly promotes M3R-stimulated insulin secretion. Examination of this noncanonical mechanism in Gnb5-/- MIN6 cells showed that cAMP, diacylglycerol, or Ca2+ levels were not significantly affected. There was no reduction in the amplitude of free Ca2+ responses in islets from the Gnb5-/- mice, but the frequency of Ca2+ oscillations induced by cholinergic agonist was lowered by more than 30%. Ablation of Gnb5 impaired M3R-stimulated phosphorylation of ERK1/2. Stimulation of the ERK pathway in Gnb5-/- cells by epidermal growth factor restored M3R-stimulated insulin release to near normal levels. Identification of the novel role of Gβ5-R7 in insulin secretion may lead to a new therapeutic approach for improving pancreatic β-cell function.
Mol Pharmacol.
2017 Sep 11
Pronin A, Wang Q, Slepak VZ.
PMID: 28893976 | DOI: 10.1124/mol.117.109678
Pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and classified as either a full or partial muscarinic agonist. Here, we report several unexpected results pertaining to its interaction with muscarinic M3 receptor (M3R). We found that pilocarpine was 1,000 times less potent in stimulating mouse eye pupil constriction than muscarinic agonists oxotremorin-M (Oxo-M) or carbachol (CCh), even though all three ligands have similar Kd values for M3R. In contrast to CCh or Oxo-M, pilocarpine does not induce Ca2+ mobilization via endogenous M3R in HEK293T or mouse insulinoma MIN6 cells. Pilocarpine also fails to stimulate insulin secretion, and instead, antagonizes insulinotropic effect of Oxo-M and CCh-induced Ca2+ upregulation. However, in HEK293T or CHO-K1 cells overexpressing M3R, pilocarpine induces Ca2+ transients like those recorded with another Gq-coupled muscarinic receptor, M1R. Stimulation of cells overexpressing M1R or M3R with CCh resulted in a similar reduction in PIP2. In contrast to CCh, pilocarpine stimulated PIP2 hydrolysis only in cells overexpressing M1R, but not M3R. Moreover, pilocarpine blocked CCh-stimulated PIP2 hydrolysis in M3R-overexpressing cells, thus, it acted as an antagonist. Pilocarpine activates ERK1/2 in MIN6 cells. The stimulatory effect on ERK1/2 was blocked by the Src family kinase inhibitor PP2, indicating that the action of pilocarpine on endogenous M3R is biased toward β-arrestin. Taken together, our findings show that pilocarpine can act as either an agonist or antagonist of M3R, depending on the cell type, expression level and signaling pathway downstream of this receptor.
Physiol Rep.
2017 Dec 12
Ronn J, Jensen EP, Wewer Albrechtsen NJ, Holst JJ, Sorensen CM.
PMID: 29233907 | DOI: 10.14814/phy2.13503
Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor.
Description | ||
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sense Example: Hs-LAG3-sense | Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe. | |
Intron# Example: Mm-Htt-intron2 | Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection | |
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G) | A mixture of multiple probe sets targeting multiple genes or transcripts | |
No-XSp Example: Hs-PDGFB-No-XMm | Does not cross detect with the species (Sp) | |
XSp Example: Rn-Pde9a-XMm | designed to cross detect with the species (Sp) | |
O# Example: Mm-Islr-O1 | Alternative design targeting different regions of the same transcript or isoforms | |
CDS Example: Hs-SLC31A-CDS | Probe targets the protein-coding sequence only | |
EnEm | Probe targets exons n and m | |
En-Em | Probe targets region from exon n to exon m | |
Retired Nomenclature | ||
tvn Example: Hs-LEPR-tv1 | Designed to target transcript variant n | |
ORF Example: Hs-ACVRL1-ORF | Probe targets open reading frame | |
UTR Example: Hs-HTT-UTR-C3 | Probe targets the untranslated region (non-protein-coding region) only | |
5UTR Example: Hs-GNRHR-5UTR | Probe targets the 5' untranslated region only | |
3UTR Example: Rn-Npy1r-3UTR | Probe targets the 3' untranslated region only | |
Pan Example: Pool | A mixture of multiple probe sets targeting multiple genes or transcripts |
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