Claude Bernard’s concept of sugar metabolism in the liver

The connection between hepatobiliary surgery and nutrition comprises the liver’s metabolic function of converting dietary nutrients into usable energy through complex biochemical pathways. The liver serves as the principal regulator of blood glucose homeostasis by converting stored glycogen into glucose. In doing so, it provides a metabolic buffer that maintains a stable internal environment for the production and controlled release of glucose into the blood, a process governed by coordinated hormonal signaling. The frailty of this regulatory system in sustaining vital functions becomes strikingly apparent when a critical mass of liver parenchyma is surgically removed after extended hepatectomy.

Claude Bernard [1813–1878], a French physiologist working in Paris at the Collège de France, laid the foundation for our understanding of these processes in the first half of the nineteenth century (1). At that time, while the external anatomy of the liver was well described, its physiological role remained largely enigmatic. It was widely believed that blood was produced within the liver -giving the organ its deep red color- and that the biliary ductal system functioned primarily as an excretory pathway for bodily waste products. The emergence of modern scientific inquiry, driven by advances in chemical and physiological sciences, redirected attention toward the investigation of the liver’s internal metabolic functions.

Claude Bernard was among the first scientists to systematically apply controlled experimental methods to physiological research in his laboratory (2). Through animal experiments, he demonstrated that the liver contains glycogen as a carbohydrate reserve and that this stored glycogen can be converted into glucose in response to metabolic demand and circulating glucose levels. He established the concept of “internal secretion” of glucose into the blood, a new insight that reframed contemporary understanding of hepatic metabolism. He proposed the concept of the milieu interieur, defined as a stable internal environment that maintains a balanced physiology independent of external influences.

Figure 1 reproduces an illustration from Bernard’s seminal work on his physiological experiments, depicting the liver and its role in sugar metabolism (3). A section of the central hepatic lobe in a dog is exposed, revealing the anatomical transition from portal venous branches coming from the intestine to hepatic venous branches draining into the inferior vena cava. The illustration epitomizes Bernard’s concept that sugars derived from ingested food are transformed within the liver parenchyma into glycogen, which is then converted into glucose and released into the blood and drained via the hepatic veins.

Figure 1 Illustration taken from Claude Bernard’s seminal work [1855] on his physiological experiments, depicting the liver and its role in sugar metabolism (3). A section of the central hepatic lobe is exposed, revealing the anatomical transition from portal to hepatic venous branches draining into the inferior vena cava. The illustration succinctly conveys Bernard’s concept that sugars derived from ingested food are transformed within the liver into glycogen. The conversion of stored glycogen to glucose is subject to the demands of the liver parenchyma. The resultant glucose is then released into the blood and subsequently drained via the hepatic veins.

Claude Bernard’s fundamental studies of glucose metabolism provided a scientific basis for understanding the liver as a central metabolic organ. His laboratory experimentation introduced a mechanism-based approach to physiological studies that shaped modern medical science.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2026-1-0010/coif). T.M.v.G. serves as an unpaid Deputy Editor-in-Chief of HepatoBiliary Surgery and Nutrition. The author has no other conflicts of interest to declare.

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References

1. Young FG. Claude Bernard and the discovery of glycogen; a century of retrospect. Br Med J 1957;1:1431-7. [Crossref] [PubMed]
2. Rheinberger HJ. Claude Bernard and life in the laboratory. Hist Philos Life Sci 2023;45:11. [Crossref] [PubMed]
3. Claude Bernard. Leçons de physiologie expérimentale appliquée à la médecine, faites au Collège de France. tome I. Paris: Baillière; 1855:(83). Available online: https://gallica.bnf.fr/ark:/12148/bpt6k6215676q