Close Interrelationships among Glucose Oxidation, Glucose-Induced ⁴⁵Ca Uptake and Insulin Release of Presumed Pancreatic β-Cell Mass

Summary

The authors have reported that alloxan, a β-cytotoxic agent, inhibited glucose oxidation and glucose-induced ⁴⁵Ca uptake of pancreatic β-cells; the non-β-cell mass was not inhibited by alloxan pretreatment. Therefore, it is feasible to assess glucose metabolism and Ca uptake in the mass composed of β-cells alone, by subtracting glucose oxidation and Ca uptake in the alloxan treated islets from the non-alloxan treated islets. In order to elucidate the interrelationship between glycolysis, glucose-induced Ca uptake and insulin release in the pancreatic β-cell mass, but not in the pancreatic islets, we investigated ¹⁴CO₂ formation from ¹⁴C-U-D-glucose, glucose-induced ⁴⁵Ca uptake and insulin release in alloxan treated and non-alloxan treated islets. In vitro incubation of collagenase digested isolated islets of Langerhans was employed. The relationships between the three parameters in the presumed pancreatic β-cell mass (¹⁴CO₂ formation from ¹⁴C-U-D-glucose, glucose-induced ⁴⁵Ca uptake and insulin release) and glucose concentration in the media were clearly sigmoidal. The threshold values of the three parameters are approximately 5 mM of glucose. The half maximum rates of ¹⁴CO₂ formation, ⁴⁵Ca uptake and insulin release required 13.4 mM, 13.6 mM and 12.8 mM of glucose, respectively. The near maximum stimulation of the three parameters was obtained at 20 mM of glucose. The highly corelated concentration-response relationship between the three parameters in the presumed pancreatic β-cell mass and glucose concentration in the media, strongly suggests that glycolysis of β-cells controls Ca mobilization in β-cells, which initiates insulin release.

Presumed β-Cell Mass - Alloxan Inhibition - Glucose Oxidation - ⁴⁵ Ca Uptake - Mechanism of Glucose-Induced Insulin Release