In vivo estimation of gluconeogenesis

PhD ceremony: Mr. S.K. Chacko, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Title: In vivo estimation of gluconeogenesis

Promotor(s): prof. P.J.J. Sauer, prof. A.L. Sunehag

Faculty: Medical Sciences

Detailed knowledge about glucose kinetics is crucial to understand metabolic diseases and to optimize nutritional strategies. As a part of this thesis, we developed a simple, accurate and reproducible method based on mass spectroscopy to estimate in vivo rates of gluconeogenesis in different populations under various conditions to address a variety of metabolic issues.

The estimation of gluconeogenesis using the newly developed method enabled us to determine that gluconeogenesis accounts for the major part of glucose production and is an ongoing process in preterm infants even when glucose is supplied at rates exceeding their normal glucose turnover rate. We also reported that the incomplete suppression of glucose production observed in preterm infants is primarily due to the contribution from gluconeogenesis. Further, our investigations determined that gluconeogenesis is not acutely regulated by either insulin or glucose concentrations in very preterm infants receiving total parenteral nutrition.

These findings are crucial to optimize nutritional strategies in premature infants. The results suggest that supplying glucose at rates corresponding to normal infant glucose turnover rate (in addition to glucose produced via gluconeogenesis utilizing the supplied gluconegenic substrates via TPN) is a potential strategy to prevent hypo/hyperglycemia in infants during their early days of life.

In this thesis we also reported that the extra glucose demands of lactation during the extended periods of fasting in lactating women are met by increasing gluconeogenesis. Further investigations of this thesis using a mice model determined that ghrelin plays a role in the regulation of gluconeogenesis/glycogenolysis and that the absence of ghrelin action has a beneficial outcome on glucose metabolism.