INHIBITION OF PANCREATIC B-CELL FUNCTION BY D-MANNOHEPTULOSE

D-mannoheptulose による膵B細胞機能の阻害

Ishibashi Fukashi

Sato Toshie

Tsubota Motoki

Kawate Ryoso

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

We have reported that alloxan inhibits glucose metabolism and glucose-induced 45Ca uptake in the pancreatic B-cells, while non-B-islet cells are not inhibited by alloxan pretreatment. Therefore, it is possible to assess glucose metabolism and Ca uptake in the B-cells by measuring these parameters in alloxan treated and non-alloxan treated islets and determining the difference. In our previous paper, we found that the glucose dose-response relationships of glucose oxidation, glucose-induced 45Ca uptake and insulin release were closely interrelated.　　In this paper we have investigated the effect of D-mannoheptulose on glucose oxidation, glucose-induced 45Ca uptake and insulin release in the B-cells by incubating isolated rat islets with and without alloxan pretreatment (20 mg/dl, for 6 minutes) in order to investigate the role of hexokinase in the regulation of glucose-induced insulin release in the pancreatic B-cells.　　In the absence of D-mannoheptulose, the threshold of the three parameters (14CO₂ formation from 14C-U-D-glucose, glucose-induced 45Ca uptake and insulin release) in the B-cells was approximately 5.5mM glucose. The half-maximal responses for each of the three parameters occurred with 11.5mM, 13.5mM and 11.7mM glucose, respectively. The maximal response for these parameters occurred with 20mM glucose. When 1.0mM D-mannoheptulose was added to glucose, the threshold for the three parameters increased to 11.0mM with half maximal responses at 15.5mM, 15.8mM and 17.0mM glucose, respectively. The maximal responses of the three parameters were obtained at 27.8mM glucose. The addition of 2.5mM D-mannoheptulose to glucose required more glucose to achieve half-maximal responses of the three parameters (27.4mM, 27.5mM and 25.5mM, respectively) with maximal responses at 38.8mM glucose.　　The inhibitions by D-mannoheptulose of glucose oxidation, glucose-induced 45Ca uptake and insulin release respectively were closely related to each other. These data indicate that hexokinase may play a regulatory role in glucose metabolism in the pancreatic B-cells resulting in the tight control of glucose-induced Ca mobilization and insulin release.

Medical sciences [ 490 ]

eng

Hiroshima University School of Medicine

[ISSN] 0018-2052

[NCID] AA00664312