This is an abbreviation of unit 8 from the Advanced Equine Nutrition course. The complete text, a video, and quiz questions are available with The Horse’s Advocate membership. You can also purchase them separately. Note: Passing the Basic Equine Nutrition Course is required before starting the Advanced Course.

Unit 8 – Cell Metabolism: Energy Used, Stored, And Removed

The Randel Cycle

The Randel Cycle, a key concept in human and animal nutrition, was first reported in 1963. It explains the intricate interaction between glucose and fatty acids. The balance of available substrate in the blood influences this interaction. It is also influenced by the demand for that substrate in the cell. Also known as the glucose-fatty acid cycle, it plays a crucial role. It determines whether a cell uses glucose or a free fatty acid (FFA) for fuel. This decision is based on the relative availability of glucose or fat in the blood.

The Randel Cycle has been the subject of numerous studies since its discovery. These studies have confirmed its results. They have also unveiled the complex interactions that govern the entry of glucose and fat into cells. Understanding this cycle is particularly significant for horses. It dictates how they utilize these fuels. This understanding influences their body composition and ability to perform. For instance, a better understanding of the Randel Cycle can help manage equine obesity. It can improve athletic performance and prevent metabolic disorders.

The Randel cycle regulates fat and glucose use in the cell. It manages their replacement through blood flow during and between daily meals. It also adjusts for seasonal food abundance and scarcity. It is a balancing process measuring the amounts of one substrate relative to the other in the blood and inside the cell. 

The goal of the cycle is to maintain an optimum efficiency of cell metabolism. This is based on the moment-by-moment flow of substrates. When you sleep, no food enters the body. This causes low blood flow of glucose, while body fat is high. As a result, there is more fat than glucose in the blood. But after a carb-filled breakfast, the opposite occurs with more blood glucose than fat. Substrates flow into the cell from greater to lesser concentrations with the cell wall in between.

The cycling between fat and glucose levels is active at every moment of life. It depends on the food eaten, the time since eating it, and the demand for the substrate. The Randel Cycle is a fine-tuned approach to using glucose and fat at the cell level.

The cycle is beneficial for the day-to-day adjustments needed for cells’ constant fuel requirements. It helps cells adapt to demands such as sleeping, running from a threat, or grazing. There are broader control mechanisms of metabolism, including hormones like insulin, glucagon, leptin, and ghrelin. More on these later, but it’s worth going into the details of insulin’s action in response to the amount of glucose in the diet in three specific situations:

• A seasonally high-sugar diet
• A seasonally low-sugar diet
• A continuously high-sugar diet

Key Points:

1. Cells choose their fuel based on the glucose and FFA amounts inside versus outside the cell. They use the Randel Cycle (glucose-fatty acid cycle) for this process.
2. The Randel Cycle causes cycling between insulin sensitivity and insulin resistance.
3. The preferred fuel use changes continuously. It depends on short-term daily activity and food availability. It also depends on long-term seasonal activity and food availability.
4. The goal of the cycle is to maintain optimum efficiency of cell metabolism. This depends on the moment-by-moment flow of substrates.
5. In the short-term, high blood glucose triggers an increase in insulin production. It decreases lipolysis and boosts insulin sensitivity. This allows glucose to become the preferred fuel inside the cell.
6. Short- or long-term low blood glucose decreases insulin production, increases lipolysis, increases insulin resistance, preserves glucose from gluconeogenesis, and allows FFAs to become the preferred fuel inside the cell,
7. Exercise depletes glycogen and increases glycolysis. It shuts down fat metabolism within the cell. It also increases insulin sensitivity, allowing for glycogen replenishment. The demand for quick energy makes the cell prefer glucose for fuel. This preference occurs even when glucose is not available from food.
8. A seasonally high-sugar diet promotes lipogenesis, allowing for survival in the upcoming season with a low-sugar diet.
9. A seasonally low-sugar diet increases insulin sensitivity. It replenishes glycogen necessary for emergencies. This diet also increases lipolysis to increase fat availability for fuel. Furthermore, it improves mitochondrial efficiency and flexibility.
10. A continuous high-sugar diet increases insulin resistance. It suppresses fat movement into the cells and increases lipogenesis. It decreases mitochondrial efficiency and flexibility. All combined, it reduces energy flux, causing Equine Metabolic Syndrome.
11. The ratio of insulin to glucagon (the I:G ratio) drives the processes of lipolysis and lipogenesis.