Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats

Naoaki Horinaka, Tang Yong Kuang, Hazel Pak, Robert Wang, Jane Jehle, Charles Kennedy, Louis Sokoloff

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.

Original languageEnglish (US)
Pages (from-to)1309-1318
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number12
StatePublished - Dec 1997

Fingerprint

Cerebrovascular Circulation
Glyburide
Caffeine
Hypoglycemia
Insulin
Adenosine
Adenosine Triphosphate
Purinergic P1 Receptor Antagonists
KATP Channels
Inosine
Hypoxanthine
Drug and Narcotic Control
Hypoglycemic Agents
Intravenous Injections

Keywords

  • [C]Iodoantipyrine
  • Adenosine receptors
  • ATP-sensitive K channels

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Horinaka, N., Kuang, T. Y., Pak, H., Wang, R., Jehle, J., Kennedy, C., & Sokoloff, L. (1997). Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. Journal of Cerebral Blood Flow and Metabolism, 17(12), 1309-1318.

Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. / Horinaka, Naoaki; Kuang, Tang Yong; Pak, Hazel; Wang, Robert; Jehle, Jane; Kennedy, Charles; Sokoloff, Louis.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 17, No. 12, 12.1997, p. 1309-1318.

Research output: Contribution to journalArticle

Horinaka, N, Kuang, TY, Pak, H, Wang, R, Jehle, J, Kennedy, C & Sokoloff, L 1997, 'Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats', Journal of Cerebral Blood Flow and Metabolism, vol. 17, no. 12, pp. 1309-1318.
Horinaka, Naoaki ; Kuang, Tang Yong ; Pak, Hazel ; Wang, Robert ; Jehle, Jane ; Kennedy, Charles ; Sokoloff, Louis. / Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. In: Journal of Cerebral Blood Flow and Metabolism. 1997 ; Vol. 17, No. 12. pp. 1309-1318.
@article{2ffe9a3114424ee493a6310c4b648f4c,
title = "Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats",
abstract = "The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51{\%} higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27{\%} increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66{\%} with glibenclamide-free artificial CSF administration, +25{\%} with 1 μmol/L glibenclamide, and almost complete blockade (+5{\%}) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.",
keywords = "[C]Iodoantipyrine, Adenosine receptors, ATP-sensitive K channels",
author = "Naoaki Horinaka and Kuang, {Tang Yong} and Hazel Pak and Robert Wang and Jane Jehle and Charles Kennedy and Louis Sokoloff",
year = "1997",
month = "12",
language = "English (US)",
volume = "17",
pages = "1309--1318",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats

AU - Horinaka, Naoaki

AU - Kuang, Tang Yong

AU - Pak, Hazel

AU - Wang, Robert

AU - Jehle, Jane

AU - Kennedy, Charles

AU - Sokoloff, Louis

PY - 1997/12

Y1 - 1997/12

N2 - The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.

AB - The possibility that adenosine and ATP-sensitive potassium channels (K(ATP)) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a K(ATP) channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and K(ATP) channels may play a role in the increases in CBF during hypoglycemia.

KW - [C]Iodoantipyrine

KW - Adenosine receptors

KW - ATP-sensitive K channels

UR - http://www.scopus.com/inward/record.url?scp=0030694276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030694276&partnerID=8YFLogxK

M3 - Article

C2 - 9397030

AN - SCOPUS:0030694276

VL - 17

SP - 1309

EP - 1318

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 12

ER -