Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells

Schmidt, Sabine; Jakab, Martin; Jav, Sarantuya; Streif, Doris; Pitschmann, Anna; Zehl, Martin; Purevsuren, Sodnomtseren; Glasl, Sabine; Ritter, Markus

doi:10.1016/j.jep.2013.08.013

Cited by 37 publications

(27 citation statements)

References 36 publications

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“…4D and E), suggesting that K ATP channels are a direct target of quercetin. Taken together we conclude that the stimulating effect of the aqueous extract of Leonurus sibiricus L. observed in INS-1E cells [1] can be attributed at least in part to its constituent quercetin. In other cell types, quercetin has also been reported to act on Ca 2+ -and K + -and channels.…”

Section: Discussionmentioning

confidence: 58%

“…In HepG2 hepatocellular carcinoma cells quercetin was found to mediate autophagy by release of Ca 2+ from intracellular stores [42] and to enhance apoptosis by induction of a positive feedback loop consisting of p53, miR-34a miRNA and SIRT1 [43]. The present study was performed to investigate short and long-term effects of quercetin and rutin on beta-cells [1,2]. While most studies which describe insulinotropic influences of flavonoids on beta-cells focus on short term effects, data on chronic exposure are lacking.…”

Section: Introductionmentioning

confidence: 97%

“…In a previous study we described the insulinotropic effects of Leonurus sibiricus L. (LS) plant extracts used in Traditional Mongolian Medicine (TMM) for the treatment of diabetes mellitus (DM) and DM-related symptoms [1]. We have demonstrated that insulin release from INS-1E cells was significantly increased in presence of aqueous as well as methanolic LS extracts.…”

Section: Introductionmentioning

confidence: 99%

“…The present study was performed to identify LS extract compounds accounting for the observed effects on beta-cell viability, insulin release and electrophysiological behavior. We focused on the flavonoid quercetin and its glycoside rutin, two phytochemicals which could be identified as constituents of LS extracts by HPLC analyses [1,2] and which are known to exert comparable effects in different cell systems.…”

Section: Introductionmentioning

confidence: 99%

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Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

Kittl

Beyreis

Tumurkhuu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Previously we described insulinotropic effects of Leonurus sibiricus L. plant extracts used for diabetes mellitus treatment in Traditional Mongolian Medicine. The flavonoid quercetin and its glycoside rutin, which exert anti-diabetic properties in vivo by interfering with insulin signaling in peripheral target tissues, are constituents of these extracts. This study was performed to better understand short- and long-term effects of quercetin and rutin on beta-cells. Methods: Cell viability, apoptosis, phospho-protein abundance and insulin release were determined using resazurin, annexin-V binding assays, Western blot and ELISA, respectively. Membrane potentials (V_mem), whole-cell Ca²⁺ (ICa)- and ATP-sensitive K⁺ (IK_ATP) currents were measured by patch clamp. Intracellular Ca²⁺ (Ca_i) levels were measured by time-lapse imaging using the ratiometric Ca²⁺ indicator Fura-2. Results: Rutin, quercetin and the phosphoinositide-3-kinase (PI3K) inhibitor LY294002 caused a dose-dependent reduction in cell viability with IC₅₀ values of ∼75 µM, ∼25 µM and ∼3.5 µM, respectively. Quercetin (50 µM) significantly increased the percentage of Annexin-V+ cells within 48 hrs. The mean cell volume (MCV) of quercetin-treated cells was significantly lower. Within 2 hrs, quercetin significantly decreased basal- and insulin-stimulated Akt(T308) phosphorylation and increased Erk1/2 phosphorylation, without affecting P-Akt(S473) abundance. Basal- and glucose-stimulated insulin release were significantly stimulated by quercetin. Quercetin significantly depolarized V_mem by ∼25 mV which was prevented by the K_ATP-channel opener diazoxide, but not by the L-type ICa inhibitor nifedipine. Quercetin significantly stimulated ICa and caused a 50% inhibition of IK_ATP. The effects on V_mem, ICa and IK_ATP rapidly reached peak values and then gradually diminished to control values within ∼1 minute. With a similar time-response quercetin induced an elevation in Ca_i which was completely abolished in the absence of Ca²⁺ in the bath solution. Rutin (50 µM) did not significantly alter the percentage of Annexin-V+ cells, MCV, Akt or Erk1/2 phosphorylation, insulin secretion, or the electrophysiological behavior of INS-1 cells. Conclusion: We conclude that quercetin acutely stimulates insulin release, presumably by transient K_ATP channel inhibition and ICa stimulation. Long term application of quercetin inhibits cell proliferation and induces apoptosis, most likely by inhibition of PI3K/Akt signaling.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

Kittl

Beyreis

Tumurkhuu

et al. 2016

Cell Physiol Biochem

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“…19 was putatively identified as lavandulifolioside, showing fragmentation described in Schmidt et al (2013). The compound was described in P. lanceolata leaves, and micropropagated plants, but could not be detected from calli so far (Budzianowska et al, 2004).…”

Section: Phenylethanoid Glycosides In P Lanceolata Callimentioning

confidence: 95%

Effects of N source concentration and NH 4 + /NO 3 − ratio on phenylethanoid glycoside pattern in tissue cultures of Plantago lanceolata L.: A metabolomics driven full-factorial experiment with LC–ESI–MS 3

et al. 2014

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HighlightsThe metabolome response to NH 4 + /NO 3 − ratio and N source was shown to be non-linear. Compared to Murashige Skoog medium, high natural product yields were observed. Simulated OFAT experimental designs led to sub-optimal yields for natural products. N source concentration is to be optimized before NH 4 + /NO 3 − ratio for high NP yield. It was shown in simulated experiments, that one-factor at a time (OFAT) experimental designs lead to suboptimal media compositions for production of many NPs, and alternative experimental designs (e.g. FF) should be preferred when optimizing medium N source for optimal yield of NPs. If using OFAT, the N source concentration is to be optimized first, followed by NH 4 + /NO 3 − ratio, as this reduces the likeliness of suboptimal yield results. Abstract

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Pancreatic β cell models for screening insulin secretagogues and cytotoxicity

Potdar,

Kharat,

Sanap

et al. 2024

J of Applied Toxicology

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In the past 2–3 decades, numerous attempts have been made to create an insulin‐secreting β cell line that maintains normal insulin secretion. However, primary β cell cultures have finite life and, therefore, cannot be used for long‐term experiments. The most widely used insulin‐secreting cell lines are Insulinoma‐1, rat insulinoma cell line, hamster pancreatic β cell line, mouse insulinoma, and β tumor cell line. Insulinoma‐derived cell lines show infinite growth in tissue culture but exhibit varying differences in their insulin responsiveness to glucose levels compared to normal β cells. Despite difficulties with β cell cultures, these cell lines have offered some useful insights in diabetes research concerning physiological functions and pathological investigations. In this review, we describe insulinoma cell lines used for drug screening, insulin secretion, cell viability, proliferation, and other relevant cellular functions. In addition, we have also incorporated recently developed human β cell lines. These cell lines have provided some helpful insights into physiological activities and pathology in diabetes research, despite challenges with β cell culturing. We propose that these cell lines could also be explored for screening Ayurvedic Rasayanas and homeopathy preparations for their cytotoxicity and insulin secretagogue activities to have evidence‐based data on alternative and complementary medicines.

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Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation of rat INS-1E insulinoma cells

Abstract: The finding that extracts from Leonurus sibiricus L. enhance insulin secretion and/or foster cell proliferation may provide possible explanations for the underlying therapeutic principles in the empirical use of LS-containing formulations in DM and DM-related disorders as applied in TMM.

Cited by 37 publications

References 36 publications

Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

Effects of N source concentration and NH 4 + /NO 3 − ratio on phenylethanoid glycoside pattern in tissue cultures of Plantago lanceolata L.: A metabolomics driven full-factorial experiment with LC–ESI–MS 3

Pancreatic β cell models for screening insulin secretagogues and cytotoxicity

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