Alterations in basal and glucose-stimulated voltage-dependent Ca2+ channel activities in pancreatic beta cells of non-insulin-dependent diabetes mellitus GK rats.
In genetically occurring non-insulin-dependent diabetes mellitus (NIDDM) model rats (GK rats), the activities of L- and T-type Ca2+ channels in pancreatic beta cells are found to be augmented, by measuring the Ba2+ currents via these channels using whole-cell patch-clamp technique, while the patterns of the current-voltage curves are indistinguishable. The hyper-responsiveness of insulin secretion to nonglucose depolarizing stimuli observed in NIDDM beta cells could be the result, therefore, of increased voltage-dependent Ca2+ channel activity. Perforated patch-clamp recordings reveal that the augmentation of L-type Ca2+ channel activity by glucose is markedly less pronounced in GK beta cells than in control beta cells, while glucose-induced augmentation of T-type Ca2+ channel activity is observed neither in the control nor in the GK beta cells. This lack of glucose-induced augmentation of L-type Ca2+ channel activity in GK beta cells might be causatively related to the selective impairment of glucose-induced insulin secretion in NIDDM beta cells, in conjunction with an insufficient plasma membrane depolarization due to impaired closure of the ATP-sensitive K+ channels caused by the disturbed intracellular glucose metabolism in NIDDM beta cells.
Kato
S
S
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Kyoto, Japan.
Ishida
H
H
Tsuura
Y
Y
Tsuji
K
K
Nishimura
M
M
Horie
M
M
Taminato
T
T
Ikehara
S
S
Odaka
H
H
Ikeda
I
I
Okada
Y
Y
Seino
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009568:Nitrendipine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012016:Reference Values
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007328:Insulin; D009568:Nitrendipine; D005947:Glucose; D011188:Potassium; D002118:Calcium