Pyruvate Tolerance Test

Glucose homeostasis is tightly controlled by the interplay of various hormones and organs. In the fasted state, glucose levels are prevented from dropping too low (hypoglycemia) through two hepatic processes: glycogenolysis, the degradation of glycogen and gluconeogenesis, the generation of glucose from non-carbohydrate carbon substrates including pyruvate and lactate (produced by anaerobic metabolism of glucose in muscles).

The intraperitoneal Pyruvate Tolerance Test (iPTT, 1-2g/kg body weight) in 15h-fasted, awake mice is a variant of the intraqperitoneal glucose tolerance test (GTT) in which pyruvate is injected instead of glucose. The pyruvate bolus elicits a glycemic excursion that reflects hepatic gluconeogenesis. Although the method can be useful in cases of severe alterations in hepatic gluconeogenesis, it is highly dependent on the variables that influence the outcome of a glucose tolerance test (GTT), including glucose-stimulated insulin secretion (GSIS) and insulin sensitivity. It is thus always necessary to analyze results from a pyruvate tolerance test in light of data obtained from a GTT, GSIS and ITT.

The gold standard method to assess gluconeogenesis is the measurement of endogenous glucose fluxes with use of tracers (e.g. during the basal period of a euglycemic hyperinsulinemic clamp).

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