The Role of the Pancreas and Liver in Blood Glucose Homeostasis

The pancreas and the liver are the main organs involved in energy metabolism and blood glucose regulation. In individuals without diabetes, these organs work in harmony to maintain normal blood glucose levels (Figure 3). The following is the “normal” healthy response in someone without T1D:

In response to rising blood glucose levels, the pancreas releases insulin. This increase in insulin quickly stops the liver from producing and secreting glucose (Figures 3 and 4). High insulin levels almost completely stop the liver from breaking down glycogen (a process called hepatic glycogenolysis) and lower the rate of gluconeogenesis (the production of glucose by the liver) by approximately 20% [38]. In addition, increased insulin in the bloodstream suppresses glucagon secretion by the pancreas and stimulates glucose uptake in peripheral tissues, such as skeletal muscle and adipose tissue.

On the other hand, if blood glucose concentration drops, even within the normal physiological range (around 80-85 mg/dL or 4.4-4.7 mmol/L), insulin secretion decreases immediately [39], reducing glucose uptake by peripheral tissues. A further decline in glucose concentration triggers the release of counterregulatory hormones, starting at a threshold of around 65-70 mg/dL or 3.6-3.9 mmol/L [39]. The primary counterregulatory hormone is glucagon, which stimulates glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the production of glucose) by the liver. Epinephrine (otherwise known as adrenaline) also plays a role in counter-regulation by stimulating gluconeogenesis and inhibiting glucose disposal by insulin-dependent tissues [40]. To a lesser extent, cortisol and growth hormone are involved in the regulation of blood glucose levels by promoting glucose production and inhibiting glucose uptake by cells [39].

This intricate feedback loop between insulin, glucagon, and other counterregulatory hormones ensures that blood glucose levels are maintained within a narrow, optimal range in people without diabetes. However, in T1D, the destruction of the insulin-producing β-cells in the pancreas disrupts this delicate balance, resulting in hyperglycaemia.