Istituto di Ingegneria Biomedica     
Ahren B., Pacini G. A Novel Approach to Assess Insulin Sensitivity Reveals No Increased Insulin Sensitivity in Mice with a Dominant-Negative Mutant Hepatocyte Nuclear Factor-1{alpha}. In: American Journal of Physiology-Regulatory Integrative and Comparative Physiology, vol. 291 pp. R131 - 7. American Physiological Society, 2006.
In phenotype experiments in mice, determination of dynamic insulin sensitivity often uses the insulin tolerance test. However, the interpretation of this test is complicated by the counterregulation occurring at low glucose. To overcome this problem, we have determine the dynamic insulin sensitivity after inhibition of endogenous insulin secretion by diazoxide (25mg/kg) in association with intravenous administration of glucose plus insulin (the DSGIT technique). Estimation of insulin sensitivity index (SI) by this technique showed good correlation to SI from a regular intravenous glucose tolerance test (r=0.87; P<0.001; n=15). With DSGIT, we evaluated dynamic insulin sensitivity in mice with a beta cell targeted dominant-negative mutation of hepatic nuclear factor (HNF)-1alpha(RIP-DN HNF-1alpha (Tg) mice). When insulin was administered exogenously at the same dose in Tg and wildtype (WT) mice, plasma insulin levels were higher in WT, indicating an increased insulin clearance in Tg mice. When the diazoxide test was employed, different doses of insulin were therefore administered (0.1 and 0.15 U/kg in WT and 0.2 and 0.25 U/kg in Tg) to achieve similar insulin levels in the groups. Minimal model analysis showed that SI was the same in the two groups (0.78+/-0.21 [10(-4) min(-1)/(pmol/l] in WT vs. 0.60+/-0.11 in Tg; P=0.45) as was the glucose elimination rate (KG)(P=0.27). We conclude that (i) the DSGIT technique determines the in vivo dynamic insulin action in mice, (ii) insulin clearance is increased in RIP-DN HNF-1alpha mice, and (iii) chronic islet dysfunction in RIP-DN HNF-1alpha mice is not compensated with increased insulin sensitivity.
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16469839&query_hl=4&itool=pubmed_docsum
DOI: 10.1152/ajpregu.00519.2005
Subject glucose effectiveness
glucose tolerance
minimal modeling
insulin action

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