The NSTZ rat model combines loss of glucose-induced insulin secretion with a reduced amount of the high Km B-cell glucose transporter, GLUT2. The purpose of this study was to determine whether the restoration of glucose-induced insulin secretion was paralleled by an increase of GLUT2. Rats injected at 2 days of age with 90 mg/kg STZ were studied at 8–13 wk of age. Insulin secretion was assessed in the isolated perfused pancreas with 16.7 mM glucose preceded by 40 min of 0 or 5.5 mM glucose. In control rats, 16.7 mM glucose caused the same large biphasic insulin response whether preceded by 0 or 5.5 mM glucose. In NSTZ rats, after 5.5 mM glucose, 16.7 mM glucose elicited virtually no rise in insulin release. In contrast, after 0 mM glucose, a large insulin response to the glucose challenge occurred that was equal to that of the control groups when the differences in B-cell mass were taken into account. However, the dose-response curve for glucose-induced insulin secretion was shifted to the left, and no second phase of insulin secretion was observed. GLUT2 was assessed after the perfusions by indirect immunofluorescence with anti-GLUT2 antisera. Both control groups showed homogenous staining in all B-cells. NSTZ rats perfused with 5.5 mM glucose had a marked diminution in GLUT2 staining. We observed no increase in GLUT2 staining in the NSTZ rats perfused with 0 mM glucose. In summary, our results show: 1) the recovered glucose responsiveness in NSTZ rats after perfusion with 0 mM glucose appears in the presence of a reduced level of GLUT2; 2) the recovered glucose-induced insulin secretion is abnormal in that the glucose dose-response curve is shifted to lower glucose concentrations and a blunted second phase occurs. These results suggest that several steps are altered in the glucose signaling pathway of glucose unresponsive B-cells from NSTZ rats, and that a reduction of GLUT2 level may be only a partial cause of the secretory defects of diabetic B-cells.
Recovery of Glucose-Induced Insulin Secretion in a Rat Model of NIDDM Is Not Accompanied by Return of the B-Cell GLUT2 Glucose Transporter
Chuan Chen, Bernard Thorens, Susan Bonner-Weir, Gordon C Weir, John L Leahy; Recovery of Glucose-Induced Insulin Secretion in a Rat Model of NIDDM Is Not Accompanied by Return of the B-Cell GLUT2 Glucose Transporter. Diabetes 1 October 1992; 41 (10): 1320–1327. https://doi.org/10.2337/diab.41.10.1320
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