Glucose Sensing and Glycolysis

Where does glucose sensing occur? Why does it occur?

Glucose sensing is mainly handled by pancreatic 𝛃-cells in the islets of Langerhans (these are clusters of endocrine cells in the pancreas that produce hormones such as insulin and glucagon). When blood glucose rises (like after eating a meal), ꞵ-cells detect this increase and respond via a chain reaction

Glucose sensing; What happen (chain reaction) when blood glucose rises?

1. Glucose enters 𝛃-cells through GLUT2 transporters.

2. Glucokinase phosphorylates glucose to glucose-6-phosphate, committing it to metabolism.

3. Glycolysis (conversion of glucose to pyruvate) ramps up →  ATP production increases

4. High ATP closes ATP-gated Kᐩ channels, depolarizing the membrane

5. This opens  (change in voltage triggers) voltage-gated Ca²ᐩ channels →   Ca²ᐩinflux triggers insulin exocytosis into the bloodstream.

6. Insulin then acts on tissues to lower blood glucose by promoting glucose uptake.

In β-cells (and in general metabolism), glycolysis is the 10-step pathway that converts…

glucose → pyruvate, producing a net of 2 ATP and 2 NADH per glucose molecule.

Glycolysis in β-cells is vital for detecting blood glucose changes… how?

because the rise in ATP/ADP ratio (ADP is generated when ATP is broken down) is the main trigger for insulin release. This increase in ATP indicates high energy availability in the cell, signaling the need for insulin secretion to lower blood glucose levels.

Glycolysis intermediates like pyruvate are also critical… because

they feed into mitochondria for oxidative phosphorylation, making even more ATP.

Hormonal Regulation of Fuel Metabolism

Hormone	Trigger	Effect on Blood Glucose	Mechanism
Insulin	High blood glucose	Decrease	Uptake of glucose into cells; storage as glycogen and fat
Glucagon	Low blood glucose	Increase	Liver glycogen breakdown and gluconeogenesis
Epinephrine	Stress/exercise	Increase	Mobilizes glucose (and fats) quickly for “fight or flight”
Cortisol	Chronic stress	Increase	Long-term gluconeogenesis, muscle breakdown (staying ready)

Well-Fed State

1. (High Blood Glucose):

   1. Insulin dominates.

   2. Muscle and fat cells pull in glucose.

   3. Liver stores glucose as glycogen or fat.