A Model of Controlled Acute Hyperglycemia in Rats: Effects of Insulin and Glucagon-Like Peptide-1 Analog

Abstract

A rodent model of controlled acute hyperglycemia that is sensitive to glucose-lowering agents insulin and glucagon-like peptide-1 (GLP-1) analog has been developed. The studies show that anesthesia could be induced in fasted rats with ketamine (100 mg/kg) plus a low dose of xylazine (5 mg/kg) without inducing the acute hyperglycemia typically associated with these agents. Under these conditions, continuous infusion of glucose (10 and 20%) via the jugular vein for 30 to 150 min induced hyperglycemia in a time-dependent fashion. Administration of "loading" boluses of glucose (0.2-0.6 ml of a 20% solution) prior to continuous infusion of 10% glucose produced more immediate and sustained hyperglycemia. Plasma levels of a variety of glucoregulatory and stress hormones such as insulin, growth hormone, glucagon, and corticosterone were determined. Only glucagon levels changed significantly during induction and maintenance of hyperglycemia. The infusion of insulin (0.1 U/kg/h) or GLP-1 analog (10 g/kg/h) effectively lowered blood glucose from its elevated levels. Insulin produced a significant increase in glucagon levels, and GLP-1 analog produced a significant increase in insulin levels without any change in other glucoregulatory and stress hormone levels. In conclusion, the present studies identified a novel approach for the induction of anesthesia and surgical manipulations without inducing hyperglycemia and further defined an approach for producing acute hyperglycemia in a controlled fashion in rodents. This model will be beneficial to study the influence of hyperglycemia in acute models of critical illness where hyperglycemia develops following the precipitating event. This model was responsive to insulin and GLP-1 analog, both of which were effective in ameliorating hyperglycemia.

Xylazine-induced reduction of tissue sensitivity to insulin leads to acute hyperglycemia in diabetic and normoglycemic monkeys

“…Stress can increase blood glucose by changing several hormones including insulin, glucagon, GLP-1, and catecholamines [11,12]. Administration of the potent α 2 agonist xylazine can result in a neurohumoral imbalance which affects blood glucose.…”

“…Administration of the potent α 2 agonist xylazine can result in a neurohumoral imbalance which affects blood glucose. In fact, several studies demonstrate that administration of xylazine increases blood glucose in various animal species, including dogs, cats, rats, and mice [12-16]. …”

“…Previous studies show that xylazine increases blood glucose in both small and large animals [12-14]. However, the effects of this drug on blood glucose homeostasis in non-human primates (NHPs) are unclear.…”

In Vitro Investigation of the Antibacterial Effect of Ketamine

“…The doses used in animal studies are calculated as 40-100 mg kg -1 and these doses are higher than the doses used in human clinical practice (2).…”

Electroacupuncture for treatment of cervicogenic headache: A meta-analysis

“…Subsequently, the changes in the blood and cerebrospinal fluid showed higher levels of beta-endorphins, indicating an increased in activity of the hypothalamus-pituitary circuit and resulted in greater release of endogenous analgesic products. Furthermore, opioid receptor motifs and tone (mu, delta, and kappa receptors) in the spinal cord of the rats also might play important roles in sustained pain relief [18,19].…”