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Corporate Overview

IsoTopics™ – April 2016

Gluconeogenesis and Glycogenolysis Measurement Review

Measurements of gluconeogenesis have been pivotal in elucidating the physiologic regulation of blood glucose homeostasis, as well as understanding the roles of glycogenolysis and gluconeogenesis in the pathophysiology of glucose metabolism in such conditions as obesity, metabolic acidosis, hypoglycemia, and diabetes. However, there is no gold-standard measure for quantifying the contribution of gluconeogenesis to total glucose production, and there has been significant controversy about specific methodologies and the ultimate result obtained. This review attempts to provide a comprehensive overview of the in vivo methodologies used to measure gluconeogenesis and glycogenolysis in humans. It discusses the real and theoretical advantages and limitations of each method and highlights the benefits of newer methodologies, such as deuterium oxide, which are simpler, more affordable, and less invasive than older techniques. 


Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to determine gluconeogenesis is by measuring the incorporation of deuterium from the body water pool into newly formed glucose. However, several techniques using radioactive and stable-labeled isotopes have been used to quantitate the contribution and regulation of gluconeogenesis in humans. Each method has its advantages, methodological assumptions, and set of propagated errors. In this review, we examine the strengths and weaknesses of the most commonly used stable isotopes methods to measure gluconeogenesis in vivo. We discuss the advantages and limitations of each method and summarize the applicability of these measurements in understanding normal and pathophysiological conditions.

Chung ST, Chacko SK, Sunehag AL, Haymond MW

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