Glucose induces calcium-dependent and calcium-independent insulin secretion from the pancreatic beta cell line MIN6.
The present study was undertaken to determine whether there are Ca2+ -dependent and -independent pathways of glucose-induced insulin secretion from the pancreatic beta cell line MIN6. Glucose at a concentration of 16.7 mmol/l caused marked increases in cellular free calcium ([Ca2+]i) and insulin secretion, which depended on glucose metabolism. When cells were pretreated with 20 mmol/l mannoheptulose, an inhibitor of glucokinase, the 16.7 mmol/l glucose induced a rise in [Ca2+]i and insulin secretion disappeared. Also, L-leucine and L-arginine increased [Ca2+]i and induced insulin secretion. Under Ca2+ -free conditions, insulin release was still induced, without any change in [Ca2+]i, by these three different stimulants. The cumulative values of insulin secretion were 13.7-29.3% of the control, which were significantly less than that in the presence of Ca2+. Cellular alkalinization occurred in response to all these stimulants, irrespective of the presence of Ca2+. Forskolin, a diterpene activator of adenylate cyclase, produced insulin secretion independently of [Ca2+]i, which accompanied cellular alkalinization. Also, a high glucose level increased cellular cyclic AMP (cAMP) production in the presence and absence of Ca2+, and the effect was diminished by approximately 73% in Ca2+ -free conditions. These results indicate that a high glucose level stimulates both Ca2+ -dependent and -independent insulin secretion from pancreatic beta cells. We suggest that the cAMP production and the cellular alkalinization participate in the Ca2+ -independent mechanism. Spermatogonial proliferation is under the control of FSH, whereas the survival of germ cells is dependent on Sertoli cell function. The observed rise in the number of mitotically inactive Ad-spermatogonia can be explained by a transformation of Ap-spermatogonia into resting Ad-spermatogonia.
Sakuma
N
N
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Ishikawa
S
S
Okada
K
K
Miyazaki
J
J
Saito
T
T
D000468:Alkalies / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D014407:Tumor Cells, Cultured
D000468:Alkalies; D007328:Insulin; D001120:Arginine; D000242:Cyclic AMP; D007930:Leucine; D005947:Glucose; D002118:Calcium