Altered functions of ion channels in diabetic beta cells.
Selective impairment of glucose-induced insulin secretion and hyper-responsiveness to arginine are known features of GK rats, a genetic model of NIDDM. We focus on the ionic mechanism underlying these phenomena using patch-clamp techniques. Pancreatic islets were isolated from male GK rats and age-matched control Wistar rats and were subjected to dispersion and culture. Single channel recordings of KATP channels were performed using either on-cell mode or inside-out patch mode. Ca2+ channel currents were recorded under conventional whole-cell mode. In GK beta cells, ATP sensitivity of KATP channels itself was not altered, although glucose-induced closure of KATP channels was severely impaired. Among substrates for fuel metabolism, only dehydroxyacetone (DHA) reproduced this anomaly. On the other hand, current densities of L-type Ca2+ channels were increased in GK beta cells. Since DHA is a known substrate for glycerol phosphate shuttle, current data suggest that major metabolic deficit of GK beta cells resides in this shuttle. On the other hand, increased L-type Ca2+ channel activities might be an ionic basis for augmented insulin response to nonglucose depolarizing stimuli in GK beta cells.
Kato
S
S
Department of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
Ishida
H
H
Tsuura
Y
Y
Seino
Y
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004553:Electric Conductivity; D005947:Glucose / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
D015220:Calcium Channels; D007473:Ion Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005947:Glucose