Insulin resistance in the St. Thomas' mixed hyperlipidaemic (SMHL) rabbit,a model for familial combined hyperlipidaemia

The St. Thomas mixed hyperlipidaemic (SMHL) rabbit exhibits an inherited hy perlipidaemia similar to that seen in familial combined hyperlipidaemia (FC HL). In this study, we investigated whether the SMHL rabbit is insulin resi stant, a condition often associated with FCHL. Six young and six mature com bined hyperlipidaemic SMHL rabbits, age/sex matched New Zealand White (NZW) control rabbits and six young hypercholesterolaemic Watanabe heritable hyp erlipidaemic (WHHL) control rabbits were fed a 0.08% (w/w) cholesterol-enri ched diet for at least 1 month prior to the start of the experiment. We per formed an oral glucose tolerance test after an overnight fast by dosing the rabbits with a solution of 1 g of glucose per kg body weight. Blood was wi thdrawn just before and 15, 30, 45, 60 and 120 min after administration of the oral glucose dose. Plasma glucose levels were similar in SMHL, WHHL and NZW rabbits throughout the oral glucose tolerance test. Fasting glucose le vels were slightly increased in WHHL rabbits but not in young and adult SMH L rabbits as compared to NZW rabbits. The area under the curve (AUC) for th e insulin response was significantly increased for both young(P < 0.05) and mature(P < 0.05) SMHL rabbits, and in WHHL rabbits, compared with NZW rabb its. The AUC for the ratio of glucose:insulin response to the glucose dose was decreased in young and mature SMHL rabbits (P < 0.05 and P < 0.01, resp ectively) and in young WHHL rabbits (P < 0.05), compared with NZW rabbits. Only WHHL rabbits showed an increased AUC for the non-esterified fatty acid response compared to NZW rabbits. Log-transformed plasma triglycerides val ues were significantly correlated with the log-transformed AUC for the insu lin response in young SMHL rabbits (r = 0.81; P < 0.05) and with the AUC fo r the insulin response in mature SMHL rabbits (I = 0.84; P < 0.05). WHHL ra bbits showed no significant correlation. In conclusion, SMHL rabbits are in sulin resistant, the severity of which appears to increase with age. Theref ore, the SMHL rabbit offers a valuable animal model in which to study the r elation between hypertriglyceridaemia and insulin resistance. (C) 2001 Else vier Science Ireland Ltd. All rights reserved.