1. ¹Department of Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
2. ²Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada
3. ³Department of Biology, Lakehead University, Thunder Bay, ON, Canada
4. ⁴Membrane Ion Channels Department, Institute of Biophysics, Bulgarian Academy of Sciences, Sofia, Bulgaria

Correspondence: Dr R Wang, MD, PhD, Department of Biology, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario, Canada P7B 5E1. E-mail: rwang@lakeheadu.ca

Received 7 May 2008; Revised 16 August 2008; Accepted 9 September 2008; Published online 10 November 2008.

Abstract

Hydrogen sulfide (H₂S) has been traditionally known for its toxic effects on living organisms. The role of H₂S in the homeostatic regulation of pancreatic insulin metabolism has been unclear. The present study is aimed at elucidating the effect of endogenously produced H₂S 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 H₂S production and insulin release were also assayed. It was found that H₂S was generated in rat pancreas islets, catalyzed predominantly by cystathionine -lyase (CSE). Pancreatic CSE expression and H₂S 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 H₂S 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 H₂S production and serum H₂S level, PPG treatment did not alter serum insulin and glucose level. Finally, H₂S significantly increased K_ATP channel activity in freshly isolated rat pancreatic -cells. It appears that insulin release is impaired in ZDF because of abnormally high pancreatic production of H₂S. New therapeutic approach for diabetes management can be devised based on our observation by inhibiting endogenous H₂S production from pancreas.