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Impact of Anesthesia During Comprehensive Assessments On Glucose Homeostasis in Diabetic NHPs

by Judith Gorski PhD, September 28, 2017 at 09:00 AM | Tags

In the clinic, either an oral glucose (oGTT) or mixed meal (MMTT) tolerance test is used to provide comprehensive assessment of glucose homeostasis in type 2 diabetic (T2D) patients. Similar procedures can also be performed preclinically in animal models.

To date, because of the technical attributes working with NHP models preclinically, the effects of anesthesia on glucose or hormonal responses during these tests were not known. In a new publication Sun et al. has demonstrated the impact of anesthesia on abnormal glucose control in a Non-Human Primate (NHP) model of spontaneously developed diabetes, a translatable model commonly used for assessing anti-diabetic therapeutics.

Glucose-Stimulated Insulin Response Enhanced by Anesthesia during ivGTT in Control NHPs

Ketamine, a commonly used injectable anesthetic in animal research, has been suggested to affect both glucose and lipid absorption. This is via the interruption of entero-gastric hormone release that are key regulators of glucose metabolism, i.e GLP-1 and GIP (1).

Contrary to the literature (2), the present data failed to show marked effects of anesthesia on the hyperglycemic response during an ivGTT in either the control or diabetic NHPs. However, the glucose-stimulated insulin response was significantly enhanced by anesthesia in the control, but not diabetic group.

The authors hypothesize the anesthesia relieved any restraining procedure-induced stress restoring the insulin response to normal/higher level, which in turn further restored/enhanced the glucose clearance rate in the control NHPs. Unfortunately, in the diabetic NHPs, the already compromised pancreatic function could not be enhanced.

MMTT Shows Anesthesia Reduces both Control Hyperglycemic and Insulin Responses

In contrast, MMTT which involves gut absorption of the glucose and nutrients, demonstrated that anesthesia reduced both hyperglycemic and insulin responses however, only in the controls, not in diabetic NHPs.

Once again, the diabetic NHPs already had severely impaired mixed meal tolerance as well as compromised pancreas function, hence responses cannot be further reduced by a slowdown in the absorption of glucose and nutrients during anesthesia.

Anesthesia Impacts ivGTT And MMTT Tests Differently in Diabetic and Normoglycemic NHPs

The authors demonstrated that both ivGTT and MMTT can serve as a powerful tool to accurately examine glucose homeostasis in the progression of diabetes in the NHP model. In addition, it was demonstrated that anesthesia may impact the degree of these tests differently in diabetic and normoglycemic NHPs.

  1. Mersmann HJ. Effect of anesthetic or analgesic drugs on lipogenic and lipolytic adipose tissue activities. Proc Soc Exp Biol Med 1983;17: 375-378.
  2. Vaughan KL et al. Comparison of anesthesia protocols for intravenous glucose tolerance testing in rhesus monkeys. J Med Primatol 2014;43: 162–168.

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