<scp>l</scp>-Cysteine Inhibits Insulin Release From the Pancreatic β-Cell

Kaneko, Yukiko; Kimura, Yoshinobu; Kimura, Hideo; Niki, Ichiro

doi:10.2337/db05-1082

Cited by 272 publications

(181 citation statements)

References 38 publications

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“…The same research team later examined the expression of CBS in HIT-T15 cells, an insulinoma pancreatic b-cell line derived from Syrian hamster, 14 and no CBS protein was shown in these cells. In contrast, Kaneko et al 15 reported the expression of CBS protein in mouse pancreatic islets and a mouse b-cell line MIN6. We have shown that CSE is the major H 2 S-generating enzyme in pancreatic islet, demonstrated by significant CSE protein expression, 11 and by our published data that PPG abolished the most H 2 S production from cultured INS-1E cells.…”

mentioning

confidence: 91%

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Yang

Jia

et al. 2009

Laboratory Investigation

197

156

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Hydrogen sulfide (H 2 S) has been traditionally known for its toxic effects on living organisms. The role of H 2 S in the homeostatic regulation of pancreatic insulin metabolism has been unclear. The present study is aimed at elucidating the effect of endogenously produced H 2 S on pancreatic insulin release and its role in diabetes development. Diabetes development in Zucker diabetic fatty (ZDF) rats was evaluated in comparison with Zucker fatty (ZF) and Zucker lean (ZL) rats. Pancreatic H 2 S production and insulin release were also assayed. It was found that H 2 S was generated in rat pancreas islets, catalyzed predominantly by cystathionine g-lyase (CSE). Pancreatic CSE expression and H 2 S production were greater in ZDF rats than in ZF or ZL rats. ZDF rats exhibited reduced serum insulin level, hyperglycemia, and insulin resistance. Inhibition of pancreatic H 2 S production in ZDF rats by intraperitoneal injection of DL-propargylglycine (PPG) for 4 weeks increased serum insulin level, lowered hyperglycemia, and reduced hemoglobin A1c level (Po0.05). Although in ZF rats it also reduced pancreatic H 2 S production and serum H 2 S level, PPG treatment did not alter serum insulin and glucose level. Finally, H 2 S significantly increased K ATP channel activity in freshly isolated rat pancreatic b-cells. It appears that insulin release is impaired in ZDF because of abnormally high pancreatic production of H 2 S. New therapeutic approach for diabetes management can be devised based on our observation by inhibiting endogenous H 2 S production from pancreas. KEYWORDS: diabetes; hydrogen sulfide; insulin release; K ATP channel; pancreas; type 2 diabetes mellitus Known as a swamp gas or 'rotten egg' gas, hydrogen sulfide (H 2 S) has yielded a public image of air pollutant for centuries. Physiological importance of H 2 S as a gasotransmitter has been realized for less than a decade. Endogenous production of H 2 S from L-cysteine is catalyzed by cystathionine b-synthase (CBS) and/or cystathionine g-lyase (CSE) with ammonium and pyruvate as co-products. 1 This process occurs in different organs and tissues, such as neuronal, vascular, and intestinal tissues. 2 Physiological concentrations of circulating H 2 S have been reported in the range of 45-300 mM. 1 At this physiological range, exogenous H 2 S has been shown to relax different vascular tissues, including isolated rat aortae and perfused mesenteric artery bed. 3-5 Altered cell proliferation or apoptosis induced by H 2 S has also been widely reported. [6][7][8][9][10] Endogenous production and physiological function of H 2 S in pancreas have been studied with identification of both CBS and CSE in rat pancreatic tissues or cloned rat pancreatic b-cell line. 11,12 In recent years, pathophysiological implications of the CSE/H 2 S system in diabetes have been reported. 12 CSE mRNA expression and H 2 S formation in rat pancreas was significantly increased after diabetes induction by streptozotocin injection. 12 CBS expression was reported in pancreatic acinar cells. 13 Y...

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confidence: 91%

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Yang

Jia

et al. 2009

Laboratory Investigation

197

156

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“…H 2 S can relax smooth muscle, protect blood vessel through inhibition of vascular remodeling, be involved in cell proliferation and apoptosis, modulate neuronal activity and regulate endocrine function. 4,[9][10][11][12] Studies have shown that H 2 S can ameliorate IRI in the heart, lung, liver, kidney and small intestine, and thus plays a general protective role against IR in different organs. [13][14][15][16][17] In a rat renal IRI model, H 2 S level was significantly decreased; however, administration of the exogenous H 2 S donor, NaHS, ameliorated IRI and improved renal function.…”

Section: Introductionmentioning

confidence: 99%

Impact of endogenous hydrogen sulfide on toll-like receptor pathway in renal ischemia/reperfusion injury in rats

et al. 2015

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In this study, we investigated the impact of endogenous hydrogen sulfide (H 2 S) on toll-like receptors (TLRs)-mediated inflammatory response and apoptosis in renal ischemia-reperfusion injury (IRI). Twenty-four male Wistar rats were randomly divided into four groups: sham, IR, IR + propargylglycine (PAG) and IR + hydroxylamine (HA). After right nephrectomy, rats were given saline for the sham and IR group, PAG for the IR + PAG group and HA for the IR + HA group, through the left renal artery for 20 min. Five minutes after drug administration, all rats except sham underwent 45 min of left renal ischemia followed by 24 h of reperfusion. Kidneys were harvested for histological and biochemical evaluation. Levels of TLRs, downstream signaling molecules and pro-inflammatory cytokines were determined by Western blot or immunohistochemistry. Hematoxylin and eosin (H&E) stained renal sections were used for histological grading of renal injury. Apoptotic cells were detected by TUNEL assay. Compared to the sham group, rats in the IR group showed higher renal levels of TLR-2, TLR-4, nuclear NF-kB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1b, IL-6, IL-18 and TNF-a (p50.05), and exhibited acute kidney injury (p50.05) and apoptosis (p50.05). Compared to the IR group, rats receiving PAG or HA showed significantly higher levels of TLR-2, TLR-4, nuclear NF-kB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1b, IL-6, IL-18 and TNF-a (p50.01), more severe acute kidney injury (p50.05) and increased apoptosis (p50.01). Thus, inflammatory response and apoptosis mediated by TLRs are involved in renal IRI. Inhibition of endogenous H 2 S significantly activated inflammatory response and apoptosis, and thus promoted renal IRI.

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“…The former is dominantly expressed in neural cells and the latter in smooth muscle [2,3]. We have recently reported that both enzymes are present in the pancreatic islets and that H 2 S, produced by L-cysteine metabolism, inhibits insulin release [4]. The effects of L-cysteine and the H 2 S donor NaHS on the beta-cells were accompanied by the inhibition of glucose metabolism and suppression of glucose-induced [Ca 2+ ] i oscillation.…”

Section: Introductionmentioning

confidence: 99%

Glucose‐induced production of hydrogen sulfide may protect the pancreatic beta‐cells from apoptotic cell death by high glucose

et al. 2008

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a b s t r a c tWe examined the expression of the major H 2 S-producing enzymes, cystathionine-b-synthase (CBS) and cystathionine-c-lyase (CSE). CBS was ubiquitously distributed in the mouse pancreas, but CSE was found only in the exocrine. Freshly isolated islets expressed CBS, while CSE was faint. However, high glucose increased the CSE expression in the beta-cells. L-Cysteine or NaHS suppressed islet cell apoptosis with high glucose, and increased glutathione content in MIN6 beta-cells. Pretreatment with L-cysteine improved the secretory responsiveness following stimulation with glucose. The CSE inhibitor DL-propargylglycine antagonized these L-cysteine effects. We suggest H 2 S may function as an 'intrinsic brake' which protects beta-cells from glucotoxicity.

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l-Cysteine Inhibits Insulin Release From the Pancreatic β-Cell

Cited by 272 publications

References 38 publications

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Impact of endogenous hydrogen sulfide on toll-like receptor pathway in renal ischemia/reperfusion injury in rats

Glucose‐induced production of hydrogen sulfide may protect the pancreatic beta‐cells from apoptotic cell death by high glucose

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