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Regulation by tolbutamide and diazoxide of the electrical activity in mouse pancreatic β ‐cells recorded in vivo
Author(s) -
Gomis Ana,
Valdeolmillos Miguel
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701628
Subject(s) - diazoxide , tolbutamide , endocrinology , medicine , depolarization , in vivo , chemistry , insulin , membrane potential , biology , biochemistry , microbiology and biotechnology
The glucose‐dependence of β‐cell electrical activity and the effects of tolbutamide and diazoxide were studied in anaesthetized mice. In untreated animals there was a direct relationship between glycaemia and the burst pattern of electrical activity. Animals with high glucose concentration showed continuous electrical activity. The application of insulin led to a steady decrease in blood glucose concentration and a transition from continuous to oscillatory activity at 7.7±0.1 m M glucose (mean±s.d.) and a subsequent transition from oscillatory to silent at 4.7±0.6 m M glucose. At physiological blood glucose concentrations the electrical activity was oscillatory. The injection of tolbutamide (1800 mg kg −1 ) transformed this oscillatory pattern into one of continuous electrical activity. The increased electrical activity was associated with a decrease in blood glucose concentration from 7.1±0.9 (control) to 5.5±1.0 m M (10 min after tolbutamide injection). The effects of tolbutamide are consistent with a direct blocking effect on the K ATP channel that leads to membrane depolarization. The injection of diazoxide (6000 mg kg −1 ) hyperpolarized the cells and transformed the oscillatory pattern into a silent one. This is consistent with a direct stimulant effect by diazoxide on the K ATP channel. The use of tolbutamide or diazoxide correspondingly led to the lengthening or shortening of the active phase of electrical activity, respectively. This indicates that in vivo , such activity can be modulated by the relative degree of activation or inhibition of the K ATP channel. These results indicate that under physiological conditions, tolbutamide and diazoxide have direct and opposite effects on the electrical activity of pancreatic β‐cells, most likely through their action on K ATP channels. This is consistent with previous work carried out on in vitro models and explains the drugs hypo‐ and hyperglycaemic effects.British Journal of Pharmacology (1998) 123 , 443–448; doi: 10.1038/sj.bjp.0701628