Type

Journal Article

Authors

Philip Newsholme
Peter R Flatt
Neville H McClenaghan
J P G Malthouse
Chandralal Hewage
Lorraine Brennan

Subjects

Biochemistry

Topics
models biological insulin secreting cells animals glucose cells cultured magnetic resonance spectroscopy sulfonylurea compounds glyburide tolbutamide carbon radioisotopes hypoglycemic agents metabolism rats pharmacology drug effects

Investigation of the effects of sulfonylurea exposure on pancreatic beta cell metabolism. (2006)

Abstract Prolonged exposure of pancreatic beta cells to the sulfonylureas glibencamide and tolbutamide induces subsequent desensitization to the actions of these drugs. The precise mechanisms underlying this desensitization remain unknown, prompting the present study, which investigated the impact of prolonged sulfonylurea exposure on glucose and energy metabolism using clonal pancreatic BRIN-BD11 beta cells. Following prolonged exposure to tolbutamide, BRIN-BD11 beta cells were incubated in the presence of [U-(13)C]glucose, and isotopomer analysis revealed that there was a change in the ratio of flux through pyruvate carboxylase (EC 6.4.1.1) and pyruvate dehydrogenase (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4). Energy status in intact BRIN-BD11 cells was determined using (31)P-NMR spectroscopy. Exposure to tolbutamide did not alter the nucleotide triphosphate levels. Collectively, data from the present study demonstrate that prolonged exposure of beta cells to tolbutamide results in changes in flux through key enzymes involved in glucose metabolism that, in turn, may impact on glucose-induced insulin secretion.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Philip Newsholme, Peter R Flatt, Neville H McClenaghan, J P G Malthouse, Chandralal Hewage, Lorraine Brennan

Experts in our system

1
Philip Newsholme
University College Dublin
Total Publications: 51
 
2
J.Paul G. Malthouse
University College Dublin
Total Publications: 71
 
3
Lorraine Brennan
University College Dublin
Total Publications: 166