Question

What metabolic and hormonal changes account for decreased gluconeogenesis in phase IV \((2 \text { to } 24\) days of starvation) of glucose homeostasis in humans?

Short answer

Answer: The main factors that contribute to the decrease in gluconeogenesis during phase IV of starvation in humans include hormonal changes such as decreased insulin levels and increased glucagon levels, a shift in the brain's energy consumption towards ketone bodies, and the preservation of lean mass, which reduces the availability of substrates for gluconeogenesis.

Step-by-step solution

1. Understanding Glucose Homeostasis and Gluconeogenesis

Glucose homeostasis refers to the balance of glucose levels in the body. Gluconeogenesis is one of the processes that contribute to glucose homeostasis by producing glucose from non-carbohydrate sources like amino acids, glycerol, and lactate. During starvation, the liver is responsible for gluconeogenesis to produce glucose for other organs, especially the brain, which requires a constant supply of glucose to function.

2. Identifying the different phases of starvation

Starvation can be divided into 4 phases: - Phase I: 0 to 4 hours, postabsorptive state, when glycogen stores are being used. - Phase II: 4 hours to 2 days, glycogen stores are depleted, and gluconeogenesis is active. - Phase III: 2 to 7 days, gluconeogenesis and ketone body production become major sources of energy. - Phase IV: 7 to 24 days and beyond, muscle breakdown decreases, and ketone bodies become the primary energy source.

3. Hormonal changes in phase IV of starvation

During phase IV of starvation, the levels of two key hormones change: insulin and glucagon. Insulin levels decrease, which reduces glucose uptake by cells and allows for more glucose to be utilized by the brain. Glucagon levels increase, which stimulates liver glycogenolysis and gluconeogenesis in the earlier phases of starvation.

4. Reduced gluconeogenesis in phase IV of starvation

As starvation progresses, the body starts preserving its lean mass, and thus the amount of available amino acids for gluconeogenesis decreases. Additionally, as ketone body production increases, the brain partially shifts to ketone bodies as an energy source, reducing its reliance on glucose and further lowering the demand for gluconeogenesis.

5. Metabolic changes in phase IV of starvation

During phase IV of starvation, the body increases lipolysis in adipose tissue, breaking down triglycerides into glycerol and fatty acids. Glycerol can be used in gluconeogenesis, but fatty acids are metabolized to produce ketone bodies (acetoacetate and β-hydroxybutyrate) in the liver. The increased production of ketone bodies helps meet the brain's energy needs, conserving glucose and decreasing the need for gluconeogenesis. In conclusion, during phase IV of starvation, decreased gluconeogenesis is a result of hormonal changes, a shift in the brain's energy consumption towards ketone bodies, and the preservation of lean mass, which reduces the availability of substrates for gluconeogenesis.

Key concepts

Glucose Homeostasis

Maintaining stable glucose levels is crucial for the proper functioning of your body, and this delicate balance is called glucose homeostasis. Imagine this as a seesaw, where on one side, you have glucose entering the bloodstream, and on the other, glucose being used or stored.

During eating, carbohydrates from food break down into glucose, which raises blood sugar levels. Insulin, a hormone released by the pancreas, helps cells absorb glucose to use for energy, or store it as glycogen in the liver and muscles, or as fat in adipose tissues. This is when the seesaw dips towards glucose storage.

Between meals or during starvation, when glucose isn't coming from food, the seesaw tips the other way. The body starts to break down glycogen into glucose, a process called glycogenolysis. But, when these stores run low, the body turns to making new glucose using non-carbohydrate sources through gluconeogenesis. The liver and kidneys work like clever chefs, transforming amino acids, lactate, and glycerol into the glucose your cells crave.

Starvation Phases

Your body goes through different phases during starvation which reflect a remarkable strategy to deal with decreased food intake.

In Phase I, you barely notice anything. The body taps into readily available glucose in the blood and then starts using glycogen stores. Think of it like using spare cash before you hit the ATM.

Phase II feels more serious—the glycogen ATM is out of cash, and gluconeogenesis kicks in. You start burning through your savings, using protein from muscles and other tissues to make glucose.

By Phase III, the body tightens its belt, maximizing the use of fats and introducing ketone bodies as a new energy currency. It's like you've started bartering goods instead of spending your savings.

Finally, in Phase IV, the body becomes miserly with its protein savings, and ketone bodies take center stage. It's like you've adjusted to a leaner budget and found ways to minimize expenses. Muscles are spared, and the brain gets used to its new fuel – ketones.

Metabolic Changes

As the body adapts to starvation, it orchestrates a series of metabolic changes that are truly a testament to human resilience. Imagine your metabolism as an adaptable power grid, switching energy sources based on availability.

Initially, the grid uses glucose. But when that runs low, your body switches circuits. Gluconeogenesis provides glucose at first, but the process is energy-intensive and involves sacrificing muscle. As starvation extends, the grid prioritizes energy conservation by reducing gluconeogenesis and shifting to a more efficient source: fat reserves. These are converted into ketone bodies, which are like a special type of electricity that can power your brain and other organs.

As the brain begins to use ketones, the demand for glucose drops, allowing your body to ease off the metabolic gas pedal of gluconeogenesis. This conserves valuable protein and lean body mass, which is akin to reducing energy consumption during peak demand in our power grid analogy.

Hormonal Regulation

The hormones in your body are like a meticulously managed crew that communicates and adjusts machinery to maintain balance during starvation. Insulin and glucagon are two key players in this complex operation.

In the beginning, insulin is the boss, directing glucose to storage sites. However, as fasting continues, insulin takes a back seat. Glucagon steps up, signalling the liver to bust open the glycogen vaults and ramp up gluconeogenesis. It's as if glucagon is unlocking emergency supplies.

As you move deeper into starvation, the insulin crew is off-duty, and glucagon's role dims too. Other hormone levels, like that of cortisol, may rise, contributing to the maintenance of blood sugar levels by influencing fat and protein breakdown. The body is now running a lean operation, with hormones signaling to conserve energy and resources. This careful hormonal regulation ensures that vital organs, particularly the brain, get enough energy to sustain basic functions.