Glucose Homeostasis: Feedback loops and regulation

Why is the regulation of blood glucose so important for the body, particularly for the brain?

+Glucose is the body’s main source of energy, especially for the brain, which cannot store glucose and depends on a constant supply from the blood.

+The brain uses only glucose to make energy (ATP), it cannot use fats directly for energy like other tissues can.

+The brain doesn’t store glucose or glycogen, so it relies on a steady blood glucose level.

+Ketones (made from fat breakdown produced by liver, specifically from fatty acids), as an backup energy source for the brain when glucose is low.

Describe the primary role of insulin glucose homeostasis. How does it facillitate glucose uptake from the bloodstream?

+The primary role of insulin in glucose homeostasis is to lower blood glucose levels by promoting the uptake of glucose from the bloodstream into body cells for energy or storage.

+After a meal, when blood glucose levels rise, insulin is released by the pancreas and travels through the bloodstream. It signals target tissues, especially muscle and fat cells, to take in glucose.

+Insulin signals GLUT4 transporters to move to the cell membrane, where they allow glucose to enter the cell for energy or storage, helping lower blood glucose to normal levels.

What are key differences between type 1 and type 2 diabetes?

+Type 1 is autoimmune disease where the body’s immune system destroys the insulin-producing beta cells in the pancreas, leading to an absolute deficiency of insulin

+ Type 2 is insulin resistance, where cells become less responsive to insulin, and often a relative deficiency in insulin secretion over time

Explain the role of glucagon in regulating blood glucose levels. Under what physiological conditions is glucagon secretion stimulated?

+Glucagon is a hormone released by the pancreas that works to increase blood glucose levels, acting as the opposite of insulin. Its main role is to ensure the body has enough glucose during fasting or between meals.

+When blood glucose levels drop, the pancreas secretes glucagon.

+Glucagon signals the liver to break down stored glycogen into glucose (glycogenolysis) and to create new glucose from other sources like amino acids (gluconeogenesis).

Outline the mechanisms within pancreatic beta cells that are triggered by increased blood glucose levels to stimulate insulin secretion.

+Increased blood glucose leads to the entry of glucose into beta cells via GLUT2 transporters.

+The event follows:

• Increased ATP Production- inside the beta cells, glucose is metabolized and creates ATP.

• Closure of KATP channels- High ATP levels bind to and close KATP channels on the beta cell membrane. This prevents K+ ions from leaving the cells

• Membrane depolarization- positive inside negative outside

• Triggers voltage gated calcium channels to open.

• The influx of calcium ions into the beta cells triggers movement and fusion of insulin-containing vesicles with the cell membrane, releasing insulin into the bloodstream through exocytosis

What are the main target tissues of insulin actions? Describe the effects of insulin on glucose metabolism in each of these tissues

+Muscle, liver, and adipose (fat) tissue.

+In muscle, insulin promotes glucose uptake and glycogen synthesis

+In liver, it promotes glycogen storage and inhibits glucose production

+In adipose tissue, it promotes glucose uptake and fat storage.

How do feedback loops contribute to the maintenance of stable blood glucose levels?

When Blood Glucose Is Too High (e.g., after eating):

1. The pancreas detects high blood glucose.

2. It releases insulin from beta cells.

3. Insulin helps cells take in glucose from the blood and signals the liver to store glucose as glycogen.

4. As blood glucose drops, insulin secretion decreases — this is the feedback part.

When Blood Glucose Is Too Low (e.g., during fasting):

1. The pancreas detects low glucose.

2. It releases glucagon from alpha cells.

3. Glucagon signals the liver to break down glycogen into glucose and release it into the blood.

4. As glucose levels rise, glucagon secretion decreases.

What role do hormones other than insulin and glucagon play in glucose homeostasis?

1. Epinephrine (Adrenaline)

• Released from: Adrenal glands

• Function: Raises blood glucose during stress or exercise by making the liver release glucose

2. Cortisol

• Released from: Adrenal cortex

• Function: Increases blood glucose during long-term stress by helping make new glucose in the liver (Gluconeogenesis)

3. Growth Hormone

• Released from: Pituitary gland

• Function: Reduces glucose uptake in muscles to keep more glucose in the blood

4. Incretins (e.g. GLP-1 and GIP)

• Released by the gut after eating.

• Help stimulate insulin release before blood glucose even rises much.

• Also slow down stomach emptying, so glucose enters the blood more gradually.

What are typical treatment for Type 1 and Type 2 diabetes?

+Type 1 insulin replacement therapy, which typically involves regular blood glucose monitoring and insulin injections. Also dietary control, and regular exercise.

+Type 2 focuses on managing insulin resisitance and improving insulin secretion through lifestyle