Glucose Tolerance and Serum Insulin Levels in an Animal Model of Obesity Induced by the Antipsychotic Drug, Sulpiride

Abstract

Ahsfruct:To assess the role of insulin in the development of obesity induced by antipsychotic drugs, a glucose tolerance test was conducted in 40 female rats during the peak of sulpiride-induced weight gain and in 40 vehicle-treated animals. The glucose area under the curve did not differ between the groups (P=0.24), however, the area under the insulin curve was significantly decreased by sulpiride (55.252.8 versus 115.6t 18.9, P=0.007). The results suggest that insulin resistance and hyperinsulinaemia are not involved in the excessive weight gain observed in this animal model of drug-induced obesity.

Antipsychotic drug-induced obesity in rats: correlation between leptin, insulin and body weight during sulpiride treatment

“…However, after 30 days of SUL administration, the area under the glucose curve significantly decreased. As discussed elsewhere, 14,15 the glucose and insulin response in SUL-treated rats shows that the BWG is not associated with hyperinsulinemia and insulin resistance. By contrast, it has been speculated that an increased insulin sensitivity may be involved in the obesity induced by this antipsychotic drug in rats.…”

“…[6][7][8][9][10][11][12][13][14][15] Therefore, we compared the leptin levels after 10 days of SUL treatment with those obtained after insulin-induced BWG in 16 animals receiving daily injections of insulin (Lilly, Mexico, DF; 5 IU s.c. for 10 days).…”

“…24 In addition, a positive correlation between serum leptin and basal insulin levels, and a negative correlation between plasma leptin and insulin sensitivity have been demonstrated. 25 Therefore, the lack of hyperinsulinemia and insulin resistance observed in AP-treated rats 14,15 should modify leptin levels during AP-induced weight gain.…”

“…[11][12][13]16 Contrary to most types of obesity in humans and rodents, [19][20][21][22] insulin resistance (defined as basal hyperinsulinemia, along with normo-or hyperglycemia) is not observed in SULtreated rats. [13][14][15] Leptin is synthesized and secreted from fat and muscle cells, and it appears to be a signal of the size of the adipose mass, glucose and lipid metabolism. Thus, leptin (and insulin) integrate the long-term homeostasis of fat stores.…”

“…[1][2][3][4][5] Prolonged administration of diverse AP also increases body weight in female rats. [6][7][8][9][10][11][12][13][14][15][16][17] During SUL treatment (a D 2 -D 3 dopamine receptor antagonist 18 ), the rats display hyperphagia, 6,13 hyperprolactinemia, [11][12][13] and disruption of the vaginal cycle suggesting drug-induced hypogonadism. [11][12][13]16 Contrary to most types of obesity in humans and rodents, [19][20][21][22] insulin resistance (defined as basal hyperinsulinemia, along with normo-or hyperglycemia) is not observed in SULtreated rats.…”