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Peroxisome proliferator-activated receptor (PPAR)-alpha controls the expression of genes involved in lipid metabolism. PPAR-alpha furthermore participates to maintain blood glucose during acute metabolic stress, as shown in PPAR-alpha-null mice, which develop severe hypoglycemia when fasted. Here, we assessed a potential role for PPAR-alpha in glucose homeostasis in response to long-term high-fat feeding. When subjected to this nutritional challenge, PPAR-alpha-null mice remained normoglycemic and normoinsulinemic, whereas wild-type mice became hyperinsulinemic (190%; P < 0.05) and slightly hyperglycemic (120%; NS). Insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) were performed to evaluate insulin resistance (IR). Under standard diet, the response to both tests was similar in wild-type and PPAR-alpha-null mice. Under high-fat diet, however, the efficiency of insulin in ITT was reduced and the amount of hyperglycemia in GTT was increased only in wild-type and not in PPAR-alpha-null mice. The IR index, calculated as the product of the areas under glucose and insulin curves in GTT, increased fourfold in high-fat-fed wild-type mice, whereas it remained unchanged in PPAR-alpha-null mice. In contrast, PPAR-alpha deficiency allowed the twofold rise in adiposity and blood leptin levels elicited by the diet. Thus, the absence of PPAR-alpha dissociates IR from high-fat diet-induced increase in adiposity. The effects of PPAR-alpha deficiency on glucose homeostasis seem not to occur via the pancreas, because glucose-stimulated insulin secretion of islets was not influenced by the PPAR-alpha genotype. These data suggest that PPAR-alpha plays a role for the development of IR in response to a Western-type high-fat diet. [ABSTRACT FROM AUTHOR]

Due to the lag between sugar intake and the beginning of recovery from hypoglycemia, it is necessary to intervene in an anticipatory way if one wants to prevent, not only detect, hypoglycemia. This article presents the principle of a hypoglycemia prevention system based on risk assessment. The risk situation can be defined as the moment when the system estimates that the glucose concentration is expected to reach a hypoglycemia threshold in less than a given time (e.g., 20 min). Since there are well-known discrepancies between blood and interstitial glucose concentrations, the aim of this experimental study performed in nondiabetic rats was first to validate this strategy, and second to determine whether it can work when the glucose concentration is estimated by a glucose sensor in subcutaneous tissue rather than in blood. We used a model of controlled decrease in blood glucose concentration. A glucose infusion, the profile of which mimicked the appearance of glucose from an intragastric load, was administered either when hypoglycemia was detected or on the basis of risk recognition. Despite the lag between the beginning of the load and that of the increase in blood glucose concentration, which was in all experiments 15-20 min, hypoglycemia was fully prevented without overshoot hyperglycemia in the groups of rats in which the glucose load was started when the hypoglycemia risk was detected, on the basis of either blood or interstitial glucose concentration. This was, of course, not the case when the same glucose load was infused at the detection of the hypoglycemia threshold.