Low-calcium diet prevents fructose-induced hyperinsulinemia and ameliorates the response to glucose load in rats

BACKGROUND Consuming a fructose-rich diet leads to hyperinsulinemia, impaired glucose tolerance, and insulin resistance. In humans, the consumption of high levels of refined sugars often coincides with a diet containing suboptimal levels of calcium. Calcium and carbohydrate metabolism interact, so there is potential for fructose to have different health outcomes depending on whether the diet is calcium-rich or calcium-poor. METHODS We evaluated the metabolic effects of feeding fructose to rats that were maintained on either a calcium-replete diet or a low-calcium diet. Growing male Sprague Dawley rats were fed diets based on the AIN-93G formulation, with the main source of carbohydrate derived either from a mixture of cornstarch and sucrose or from fructose. Half the rats given each carbohydrate source were fed calcium at recommended levels (125 mmol/kg Ca(2+)); the others were fed a diet low in calcium (25 mmol/kg Ca(2+)). At various times, glucose and insulin tolerance tests were conducted to assess glucose metabolism. RESULTS Rats fed low-calcium diet had lower fasting insulin levels irrespective of the carbohydrate source they ate. They had a normal glycemic response to a glucose load and did not develop hyperinsulinemia under conditions of fructose feeding. The drop in blood glucose levels in response to insulin injection was larger in rats fed low-calcium diet than in those fed calcium-replete diet. CONCLUSIONS Low-calcium diet prevented fructose-induced hyperinsulinemia and improved glucose handling under conditions of fructose feeding. Potential mechanisms underlying these effects of the low-calcium diet remain to be determined, but possibilities include impairment of insulin release from the pancreas and improved peripheral insulin sensitivity.