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Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats
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Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats
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Journal Article
Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats
2009
Overview
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
γ
-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 (
P
<0.05). 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
β
-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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
Alkynes - administration & dosage
/ Animals
/ Biological and medical sciences
/ Cystathionine gamma-Lyase - metabolism
/ Diabetes Mellitus - etiology
/ Diabetes Mellitus - metabolism
/ Diabetes Mellitus - physiopathology
/ Fundamental and applied biological sciences. Psychology
/ Glycine - administration & dosage
/ Glycine - analogs & derivatives
/ Hydrogen Sulfide - antagonists & inhibitors
/ Hydrogen Sulfide - metabolism
/ Investigative techniques, diagnostic techniques (general aspects)
/ Islets of Langerhans - metabolism
/ Male
/ Medicine
/ Rats
