ORIGINAL PAPER Effects of diet supplementation with olive oil and guar upon fructose-induced insulin resistance in normal rats P. G. Prieto Æ J. Cancelas Æ P. Moreno Æ M. L. Villanueva-Pen ˜ acarrillo Æ W. J. Malaisse Æ I. Valverde Received: 18 May 2007 / Accepted: 27 June 2007 / Published online: 20 July 2007 Ó Humana Press Inc. 2007 Abstract Exposure of normal rats to fructose-containing drinking water represents a current model of insulin resistance. The major aim of the present study was to assess the possible effect of diet supplementation with either olive oil or guar upon the metabolic consequences of exposure to exogenous fructose. For this purpose, the changes in body weight, plasma D-glucose and insulin concentrations, and D-glucose infusion rate during a hyperinsulinemic-eugly- cemic clamp were measured after 65 days exposure to exogenous fructose and either olive oil- or guar-enriched diet. The results were compared to those previously col- lected in control animals exposed for the same period to either tap water or the fructose-containing drinking water and a standard diet. Diet supplementation with olive oil or guar failed to affect the increase in the insulinogenic index and the decrease in insulin sensitivity and fasted/fed ratio for plasma insulin concentration caused by exogenous fructose. In the rats exposed to exogenous fructose, the olive oil-fed rats differed from other animals by the ab- sence of a decrease in food intake and body weight gain, whilst the guar-fed rats differed from other animals in a lower plasma D-glucose concentration in fed state and an absence, at day 65, of a higher plasma D-glucose concen- tration than that at day 0 measured in after overnight fasting state. These findings argue in favour of guar, rather than olive oil, to oppose the effect of exogenous fructose on glucose homeostasis. Keywords Fructose-enriched diet Á HOMA Á Euglycemic-hyperinsulinemic clamp Á Insulin secretion Á Insulin resistance Introduction To improve glucose homeostasis, exposure to diets sup- plemented with several specific nutrients such as olive oil [1–3], long-chain polyunsaturated x3 fatty acids [4–7] or guar [8–11], amongst others, is under current investigation. It was proposed that diets containing an increased pro- portion of monounsaturated fatty acids, compared to car- bohydrates, improve glycemic control and lipid metabolism [12–14]. Recently, it has been reported that an olive oil-enriched diet improves insulin-response to oral glucose and glucose tolerance [15]. Guar gum intake immediately decreases postprandial plasma glucose and insulin concentrations in either normal human subjects [16–21] or patients with type 2 diabetes [9]; it was also reported that in normal subjects [22] or patients with type 1 or type 2 diabetes [23–26], long-term ingestion of guar-supplemented diet lowers fasting blood glucose, haemoglobin A1C, cholesterol and triglycerides, decreases systolic and diastolic blood pressure, increases insulin sensitivity and improves postprandial glucose tol- erance. Guar gum-enriched diet improves glucose tolerance and insulin sensitivity in normal [27, 28] and streptozoto- cin-induced diabetic [29] rats, or in rats rendered glucose intolerant and hypertriglyceridemic by fructose feeding [10], and lowers postprandial insulinemia in either normal animals or rats exposed to fructose-based diet. P. G. Prieto Á J. Cancelas Á P. Moreno Á M. L. Villanueva- Pen ˜acarrillo Á I. Valverde (&) Department of Metabolism, Nutrition and Hormones, Fundacı ´o ´n Jime ´nez Dı ´az, Avda. Reyes Cato ´licos 2, Madrid 28040, Spain e-mail: ivalverde@fjd.es W. J. Malaisse Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium Endocr (2007) 31:294–299 DOI 10.1007/s12020-007-0038-3