Recovery of glucose-induced insulin secretion in a rat model of NIDDM is not accompanied by return of the B-cell GLUT2 glucose transporter.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
C
C
Research Division, Joslin Diabetes Center, Boston, Massachusetts.
Thorens
B
B
Bonner-Weir
S
S
Weir
G C
GC
Leahy
J L
JL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010179:Pancreas / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005947:Glucose