Glucose and alpha-ketoisocaproate induce transient inward currents in rat pancreatic beta cells.
The perforated patch technique was used to study changes in membrane potential and whole-cell currents in single isolated rat pancreatic beta-cells during stimulation with glucose or alpha-ketoisocaproate. Increasing the glucose concentration from 4 to 20 mmol/l, or addition of 15 mmol/l alpha-ketoisocaproate, caused depolarization and, in most cases, initiation of action potentials. Under voltage-clamp conditions close to a potassium equilibrium potential (EK) (-60 to -70 mV) these effects were accompanied by the appearance of transient inward currents. These transient currents resembled those elicited during cell swelling in response to a 10% hypotonic bath solution, a manoeuvre which also caused beta-cell depolarization and electrical activity. Tolbutamide (0.2 mmol/l), in the absence of glucose depolarized beta-cells but did not induce transient inward currents. Nutrient-induced electrical activity and inward currents were abolished by the anion channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid, compounds which also inhibited glucose-induced insulin release. It is concluded that nutrient secretagogues induce transient inward currents in isolated rat beta-cells, possibly by activating a volume-sensitive anion conductance. These inward currents could enhance the intensity of electrical, and hence secretory, activity in the beta-cell during nutrient stimulation.
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School of Biological Sciences, University of Manchester, UK.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007651:Keto Acids / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D007473:Ion Channels; D007651:Keto Acids; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C013082:alpha-ketoisocaproic acid; D014044:Tolbutamide; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium