MURINE INSULINOMA CELL-LINE WITH NORMAL GLUCOSE-REGULATED INSULIN-SECRETION

Pancreatic betaTC lines derived from insulinomas arising in transgenic mice expressing SV40 Tag under control of the insulin promoter manife st a differentiated beta-cell phenotype and secrete insulin in respons e to glucose. Previously reported betaTC lines respond to subphysiolog ical extracellular glucose levels compared with normal beta-cells. Rec ently, several betaTC lines were developed with normal glucose-regulat ed insulin secretion from insulinomas obtained by breeding of the RIP- Tag transgene from the original C57Bl/6 mouse strain into the C3HeB/Fe J strain. One of these betaTC lines, betaTC7, was characterized in det ail. betaTC7 cells express GLUT2 and have levels of glucokinase and he xokinase activity similar to those of normal islets. As a result these cells exhibit a normal glucose concentration dependency for glycolysi s and insulin secretion, thus representing an accurate model of beta-c ell function. On continuous propagation in culture, betaTC7 cells acqu ired a response to lower extracellular glucose levels. This change was associated with a fourfold increase in hexokinase activity, without s ignificant changes in glucokinase activity and glucose uptake rates. T hese findings suggest an important role for glucose phosphorylation ra tes in regulation of the beta-cell insulin secretory response to gluco se.