Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Abstract

Acute administration of olanzapine rapidly elevates blood glucose levels. However, the mechanism underlying the rapid development of hyperglycemia with the administration of olanzapine remains unclear. The aim of the present study was to clarify the mechanism underlying olanzapine-induced acute hyperglycemia. Male Wistar rats received an intravenous infusion of saline (control) or olanzapine 2.5, 5, or 10 mg/kg. Blood samples were obtained periodically after olanzapine infusion to determine serum concentrations of glucose, olanzapine, and several endogenous substances. In a separate experiment, rats received an intravenous injection of propranolol (2 mg/kg) 30 min before infusion of olanzapine (10 mg/kg). The intravenous infusion of olanzapine induced dose-dependent increases in the serum concentrations of glucose, epinephrine, and insulin. Pretreatment with propranolol suppressed olanzapine-induced elevations in the serum concentration of glucose, but did not affect the serum concentration of olanzapine or olanzapine-induced increase in the serum concentration of epinephrine. Although the serum concentration of corticosterone increased after administration of olanzapine, no significant differences were observed among the olanzapine dose groups. Furthermore, administration of olanzapine did not affect the serum concentration of glucagon or histamine. We developed a pharmacokinetic-pharmacodynamic model assuming that the olanzapine-induced secretion of epinephrine leads to elevated serum glucose concentrations. This model appeared to satisfactorily characterize olanzapine-induced hyperglycemia. In conclusion, a single intravenous dose of olanzapine dosedependently increased the serum concentration of glucose in rats, and epinephrine plays a role in olanzapineinduced acute hyperglycemia.

Clozapine-Induced Acute Hyperglycemia Is Accompanied with Elevated Serum Concentrations of Adrenaline and Glucagon in Rats

“…Our previous reports demonstrated that fluoroquinolone antimicrobial agents can induce histamine release leading to an increase in serum epinephrine concentrations and hyperglycemia. [7][8][9] In contrast, a single intravenous injection of clozapine increased the serum glucose levels without histamine release. Olanzapine also induced hyperglycemia without affecting the serum concentration of histamine.…”

“…We previously reported that novel fluoroquinolone antimicrobial agents such as gatifloxacin, levofloxacin, and moxifloxacin increased serum glucose concentrations in rats, in association with the induction of histamine release by these drugs, leading to elevations in serum adrenaline concentrations. [6][7][8][9] In contrast, a single intravenous injection of olanzapine increased the serum glucose and adrenaline levels without histamine release. 10) These results suggest that the mechanisms responsible for drug-induced elevations in serum glucose levels vary among these drugs.…”

Cardiovascular side effects of neuropsychiatric medication: an update

“…This caused acceleration of atherosclerosis and the onset of ischemic diseases. These drugs have been involved in weight gain, abdominal obesity, dyslipidemias and have increased insulin resistance, hepatic glucose production and the level of blood sugar [47][48][49] .…”

“…These studies demonstrated that serum glucose concentrations have been greater because of a higher hepatic gluconeogenesis via the sympatethic nervous system. Also, changing the fatty acid profile by increasing saturated fats could play a role in insulin resistance 49 .…”

Psychopharmaka-induzierte unerwünschte Wirkungen in der Ernährungstherapie

“…▶ Tab. 2 Unerwünschte metabolische Wirkungen der in Deutschland am häufigsten verordneten Antipsychotika auf der Basis der Angaben in Fachinformationen (modifiziert nach [2,34,35] [42]. Zudem scheint Olanzapin das Verhältnis der Fettsäuren (gesättigt/ungesättigt) zu modifizieren, wodurch eine Insulinresistenz begünstigt wird [43].…”