Regulation by glucose of oscillatory electrical activity and 5-HT/insulin release from single mouse pancreatic islets in absence of functional K(ATP) channels.
The glucose sensitivity of bursting electrical activity and pulsatile insulin release from pancreatic islets was determined in absence of functional K(ATP) channels. Membrane potential, [Ca(2+)](i) and 5-HT/insulin release were measured by intracellular recording, fura-2 fluorescence and 5-HT amperometry, respectively. Single mouse islets, bathed in tolbutamide or glibenclamide and high extracellular Ca(2+) (Ca(2+)(o)), displayed bursting activity and concomitant fast [Ca(2+)](i) and 5-HT/insulin oscillations. Sulphonylurea block of K(ATP) channel current was unaffected by raising Ca(2+)(o). Raising glucose or alpha-ketoisocaproic acid (KIC) concentration from 3 to 30 mM increased spiking activity and burst plateau duration. Staurosporine did not impair glucose potentiation of electrical activity, ruling out the involvement of serine/threonine kinases. Glucose enhanced both [Ca(2+)](i) and 5-HT/insulin oscillatory activity, causing a approximately 3-fold increase in overall 5-HT release rate. Cells lacking bursting activity in high Ca(2+)(o) and low glucose (or KIC) developed a pattern of intensified spiking in response to 11 mM glucose. It is concluded that beta-cells exhibit graded oscillatory electrical and secretory responses to glucose in absence of functional K(ATP) channels. This suggests that, under physiological conditions, early glucose sensing may involve other channels besides the K(ATP) channel.
Rosário
Luís M
LM
Center for Neurosciences and Cell Biology, University of Coimbra, Portugal.
Barbosa
Rui M
RM
Antunes
Célia M
CM
Baldeiras
Inês E
IE
Silva
Amélia M
AM
Tomé
Angelo R
AR
Santos
Rosa M
RM
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005947:Glucose / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007651:Keto Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D007651:Keto Acids; D015221:Potassium Channels; D012701:Serotonin; C013082:alpha-ketoisocaproic acid; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005947:Glucose; D005905:Glyburide; D002118:Calcium