PMID- 10696086
OWN - NLM
STAT- MEDLINE
DCOM- 20000504
LR  - 20181217
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 129
IP  - 5
DP  - 2000 Mar
TI  - Exposure to glibenclamide increases rat beta cells sensitivity to glucose.
PG  - 887-92
AB  - An increased sensitivity to glucose was observed in islets pre-exposed for 1 h to 
      glibenclamide (0.1 micromol 1(-1)), but not to tolbutamide (100 micromol l(-1)), 
      as indicated by a shift to the left of the dose-response curve (EC(50) at 
      5.8+/-0.3 mmol l(-1) glucose vs 10.6+/-0.8 in control islets; n=11, P<0.005). 
      According to this secretory pattern also glucose utilization at 2.5 and 5.0 mmol 
      l(-1) glucose was higher in islets exposed to glibenclamide. Since binding to 
      mitochondria results in an increased enzyme activity, we measured hexokinase (HK) 
      and glucokinase (GK) activity both in a cytosolic and in a mitochondrion-enriched 
      fractions. Cytosolic hexokinase activity was similar in islets exposed to 
      glibenclamide and in control islets but mitochondrial hexokinase activity was 
      significantly increased after exposure to glibenclamide (124+/-7 vs 51+/-9 nmol 
      microgram prot(-1) 90 min(-1), P<0.01), with no change in the enzyme protein 
      content. In contrast, glucokinase activity in the two groups of islets was 
      similar. When in islets < exposed to glibenclamide hexokinase binding to 
      mitochondria was inhibited by the addition of 20 nmol l(-1) 
      dicyclohexylcarbodiimide (DCC), no increase of glucose sensitivity was observed 
      (EC(50) 10.9+/-1.3 mmol l(-1) glucose, n=3, similar to that of control islets). 
      These data indicate that a 1 h exposure to glibenclamide causes the beta cell to 
      become more sensitive to glucose. This increased sensitivity is associated with 
      (and may be due to) an increased hexokinase activity, in particular the 
      mitochondrial-bound, more active, form. This mechanism may contribute to the 
      hypoglycemic action of this drug.
FAU - Patane, G
AU  - Patane G
AD  - Institute of Internal Medicine, Endocrinology and Metabolism, 'Signorelli' 
      Diabetes Center, University of Catania, Ospedale Garibaldi, Catania, Italy.
FAU - Piro, S
AU  - Piro S
FAU - Anello, M
AU  - Anello M
FAU - Rabuazzo, A M
AU  - Rabuazzo AM
FAU - Vigneri, R
AU  - Vigneri R
FAU - Purrello, F
AU  - Purrello F
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Keto Acids)
RN  - 538-75-0 (Dicyclohexylcarbodiimide)
RN  - 816-66-0 (alpha-ketoisocaproic acid)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
RN  - SX6K58TVWC (Glyburide)
SB  - IM
MH  - Animals
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Dicyclohexylcarbodiimide/pharmacology
MH  - Glucose/metabolism/*pharmacology
MH  - Glyburide/*pharmacology
MH  - Hexokinase/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/*drug effects/metabolism
MH  - Keto Acids/pharmacology
MH  - Male
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
MH  - Subcellular Fractions/drug effects/metabolism
PMC - PMC1571914
EDAT- 2000/03/01 09:00
MHDA- 2000/05/08 09:00
PMCR- 2001/03/01
CRDT- 2000/03/01 09:00
PHST- 2000/03/01 09:00 [pubmed]
PHST- 2000/05/08 09:00 [medline]
PHST- 2000/03/01 09:00 [entrez]
PHST- 2001/03/01 00:00 [pmc-release]
AID - 0703131 [pii]
AID - 10.1038/sj.bjp.0703131 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2000 Mar;129(5):887-92. doi: 10.1038/sj.bjp.0703131.