Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis

Yusuf, Moshood A.; Huat, Benny Tan Kwong; Hsu, Annie; Whiteman, Matthew; Bhatia, Madhav; Moore, Philip K.

doi:10.1016/j.bbrc.2005.06.021

Cited by 178 publications

(173 citation statements)

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“…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 Yusuf et al 12 also detected the expression of CBS mRNA in mouse pancreas but whether this expression was located to pancreatic islets or other parts of the pancreas was not clear.…”

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confidence: 88%

“…[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.…”

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confidence: 99%

“…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.…”

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confidence: 99%

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

Yang

Jia

et al. 2009

Laboratory Investigation

199

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

Yang

Jia

et al. 2009

Laboratory Investigation

199

156

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“…Human brain homogenates contain 50-160 mM H 2 S (Goodwin et al 1989) while substantial amounts (about 50-100 mM) are also found in human (Richardson et al 2000) and rat (Zhao et al 2001) serum. In experimental diabetes animal models, both streptozotocin and Zucker diabetic fatty rats had significantly higher H 2 S formation in the pancreas (Jia et al 2004, Yusuf et al 2005. Increased CSE and CBS activity in diabetic animals and human have also been observed in different laboratories (Wijekoon et al 2004, Herrmann et al 2005.…”

Section: Introductionmentioning

confidence: 98%

“…H 2 S is endogenously produced from the amino acid, L-cysteine, by two key enzymes that are involved in the trans-sulphuration pathway, cystathionine-g-lyase (CSE) and cystathionine-b-synthetase (CBS; Kamoun 2004). These two enzymes are distributed in a wide range of tissues, including the pancreas (Bhatia et al 2005), and their expression and activities have been shown to be altered in a variety of pathophysiological conditions (Mok et al 2004, Yan et al 2004, Bhatia et al 2005, Li et al 2005. Human brain homogenates contain 50-160 mM H 2 S (Goodwin et al 1989) while substantial amounts (about 50-100 mM) are also found in human (Richardson et al 2000) and rat (Zhao et al 2001) serum.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

Ali¹,

Whiteman²,

Low³

et al. 2007

Journal of Endocrinology

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Hydrogen sulphide (H 2 S), a naturally occurring gas exerts physiological effects by opening K ATP channels. Anti-diabetic drugs (e.g. glibenclamide) block K ATP channels and abrogate H 2 S-mediated physiological responses which suggest that H 2 S may also regulate insulin secretion by pancreatic b-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 mM) and the K ATP channeldriven pathway of insulin secretion was tracked with various fluorescent probes. The concentration of insulin released from HIT-T15 cells decreased significantly after NaHS exposure and this effect was reversed by the addition of glibenclamide (10 mM). Cell viability and intracellular ATP and glutathione (GSH) levels remained unchanged, suggesting that changes in insulin secretion were not ATP linked or redox dependent. Through fluorescence imaging studies, it was found that K C efflux occurs in cells exposed to NaHS. The hyperpolarised cell membrane, a result of K C leaving the cell, prevents the opening of voltage-gated Ca 2C channels. This subsequently prevents Ca 2C influx and the release of insulin from HIT-T15 cells. This data suggest that H 2 S reduces insulin secretion by a K ATP channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H 2 S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H 2 S production in streptozotocin-diabetic rats.

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Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

Szabó

2010

Burger's Medicinal Chemistry and Drug Discovery

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Nitric oxide ( NO ), carbon monoxide ( CO ), and hydrogen sulfide ( H 2 S ) are the main endogenous gasotransmitters. These gases are produced by the body by enzymatic reactions and serve physiological regulatory purposes including vasodilatation and anti‐inflammatory effects. Over the past decades, multiple approaches have been identified for the therapeutic exploitation of these three gasotransmitters, based on inhalation of the gases and/or the parenteral or enteral administration of various formulations of these molecules or their prodrugs. Here we overview the medicinal chemistry and the therapeutic applications of NO, CO, and H 2 S and their prodrugs. Inhaled NO is used clinically to selectively dilate the pulmonary vasculature in the therapy of the primary pulmonary hypertension of the newborn. Organic nitrates such as glyceryl trinitrate or nitroglycerin are used in the therapy of acute and chronic angina. Sodium nitroprusside is used to counteract acute hypertensive crisis. Another class of clinical‐stage NO donor drugs is the sydnonimines (molsidomine, linsidomine). Additional classes of NO donors include diazeniumdiolates (NONOates) and S ‐nitrosothiols, with beneficial effects in various preclinical models of disease. With respect to CO, the main therapeutic approaches are CO inhalation (currently in clinical trials for the experimental therapy of delayed graft function associated with kidney transplantation) and carbon monoxide releasing compounds of various classes (in preclinical stage). With respect to H 2 S, a parenteral injectable formulation of the gas is currently is Phase I trials. Several classes of H 2 S donor molecules have also been identified, which are used in preclinical studies.

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Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis

Cited by 178 publications

References 35 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

Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs

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Streptozotocin-induced diabetes in the rat is associated with enhanced tissue hydrogen sulfide biosynthesis

Cited by 178 publications

References 35 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

Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH2Sand their Prodrugs

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Medicinal Chemistry and Therapeutic Applications of the GasotransmittersNO,CO, andH₂Sand their Prodrugs