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Articles in PresS, published online ahead of print June 11, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00199.2002
Submitted on May 8, 2002
Accepted on June 10, 2002
1 Medicine, Lund University, LUND, Sweden
2 Systems Science and Biomedical Engineering, LADSEB-CNR, Padua, Italy
* To whom correspondence should be addressed. E-mail: Bo.Ahren{at}med.lu.se.
This study evaluated the relative contribution of insulin-dependent mechanisms versus mechanisms independent on dynamic insulin for-independent glucose uptake to glucose intolerance induced by high-fat diet. C57BL/6J mice underwent frequently sampled IVGTT (glucose 1 g/kg) at 1 week, 1, 3 and 10 months after initiation of a high-fat diet (58% fat; control diet 11% fat) to measure glucose effectiveness (SG) and disposition index (DI), i.e., insulin sensitivity (SI) times early or total insulin secretion. Glucose disappearance (KG) and SI were reduced in high-fat fed mice at all time points. Total (50 min) insulin secretion was sufficiently increased at all time points to compensate for the reduced SI, as judged by normal DI50 min. In contrast, early (10 min) insulin secretion was not sufficiently increased; DI10 min was reduced after 1, 3 and 10 months. SG was reduced after 1 week; the reduction persisted throughout the study period. Thus, glucose intolerance induced by high-fat diet is in early phases solely explained by reduced glucose effectiveness, whereas insuffi-cient early insulin secretion is of importance after long-term feeding.
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