blood glucose

What is the clinical definition of hypoglycemia and what is the primary cause of its symptoms? [2]

Hypoglycaemia is typically defined as a blood glucose level

What are the typical thresholds for hyperglycemia and at what level does it become a medical emergency? [2]

Hyperglycaemia is typically >12.0 mmol/L. At levels >20.0 mmol/L, it becomes a ketoacidosis emergency, where the body produces acidic ketones due to a lack of insulin action. [2]

What are the long-term micro- and macrovascular complications associated with chronic hyperglycemia? [2]

Chronic high blood glucose leads to neuropathy (nerve damage), nephropathy (kidney damage), and damage to both small (microvascular) and large (macrovascular) blood vessels. [2]

What clinical laboratory test is used to measure long-term glucose control and what does it represent? [2]

The ( \text{HbA}_{1c} ) test measures glycated haemoglobin. It reflects the average blood glucose levels over the past 2–3 months by measuring how much sugar is chemically bonded to red blood cells. [2]

How do glycaemic fluctuations contribute to diabetic complications? [2]

Rapid changes from low to high (and vice-versa) trigger inflammatory and oxidative stress responses, which can underlie and worsen diabetic complications. [2]

What are the three primary sources of glucose for the body? [3]

1. Food (dietary intake)
   2. Glycogenolysis (breakdown of stored glycogen)
   3. Gluconeogenesis (synthesis of glucose from non-carbohydrate sources). [3]

Define the metabolic pathways of glycogenesis and glycogenolysis. [3]

Glycogenesis: The process of converting glucose into glycogen for storage in the liver and muscle.
Glycogenolysis: The process of breaking down glycogen back into glucose for energy. [3]

Which organs are primarily responsible for the metabolic "disposal" or storage of glucose? [3]

The muscle (for metabolism/energy) and the liver (for glycogenesis/storage). [3]

What four major anatomical systems are involved in maintaining glucose homeostasis? [4]

1. Brain (central regulation)
   2. Liver (storage and production)
   3. Pancreas (hormonal control)
   4. Gut/Intestines (absorption and signaling). [4]

List the five types of endocrine cells in the pancreatic islets and their relative percentages. [5]

1. Beta cells (70%)
   2. Alpha cells (20%)
   3. Delta cells (

Match the pancreatic islet cells to the hormones they secrete. [5]

Beta cells: Insulin
Alpha cells: Glucagon
Delta cells: Somatostatin
Gamma cells: Pancreatic polypeptide
Epsilon cells: Ghrelin [5]

Describe the first step of glucose sensing in the pancreatic beta cell. [6]

Glucose enters the beta cell via the GLUT1 transporter (glucose transporter 1). Once inside, it is metabolized by the mitochondria to produce ATP. [6]

How does increased ATP within a beta cell lead to insulin release? [6]

1. High ATP levels cause the ( \text{K}_{\text{ATP}} ) channel (ATP-sensitive potassium channel) to close.
   2. This closure changes the cell membrane potential (depolarization).
   3. Depolarization opens voltage-gated ( \ce{Ca^{2+}} ) channels.
   4. Influx of ( \ce{Ca^{2+}} ) triggers the exocytosis of Insulin vesicles. [6]

What is the "Cephalic response" in glucose control? [7]

It is a pre-emptive rise in Insulin triggered by the brain (sight/smell/thought of food) via the parasympathetic nervous system acting on ( \text{m}_3\text{AChR} ) (Muscarinic type 3 acetylcholine receptors). [7]

How does the sympathetic nervous system regulate insulin and glucagon during high vs. low glucose states? [7]

High glucose: Sympathetic activation of \( \alpha_2\text{AR} \) (Alpha-2 adrenergic receptors) can modulate insulin release.
Low glucose: Sympathetic activation of \( \beta_2\text{AR} \) (Beta-2 adrenergic receptors) stimulates Glucagon release. [7]

Which autonomic receptors on Alpha cells stimulate glucagon release during low blood glucose? [7]

1. ( \beta2\text{AR} ) (Sympathetic)
   2. ( \text{m}3\text{AChR} ) (Parasympathetic) [7]

Which metabolic pathways does insulin promote to lower blood glucose? [8]

Insulin promotes Glycolysis (glucose breakdown), Glycogenesis (glycogen storage), Lipogenesis (fat storage), and Protein synthesis. [8]

Which hormones are considered "counter-regulatory" to insulin, and what pathways do they promote? [8]

Glucagon, Adrenaline, and Cortisol. They promote Glycogenolysis (breaking down glycogen), Gluconeogenesis (creating new glucose), and Lipolysis (breaking down fats). [8]

How do Insulin and Glucagon interact as a "switch" for glucose production? [8]

Insulin inhibits glycogenolysis and gluconeogenesis while promoting storage.
Glucagon inhibits glycolysis and glycogenesis while promoting glucose release. [8]

Describe the basic structure and activation of the insulin receptor. [9]

The insulin receptor consists of Chain A and Chain B. Insulin binds to Site 1 and Site 2, causing the two chains to crosslink and unfold, which activates the intracellular Kinase domain. [9]

What is the primary "second messenger" signaling hub for insulin action inside the cell? [10]

The signaling cascade moves from the IRS (Insulin Receptor Substrate) to AKT (also known as Protein Kinase B). [10]

List four major cellular effects of AKT activation in the insulin pathway. [10]

1. GLUT4 translocation: Movement of glucose transporters to the cell membrane for Glucose uptake (primarily in muscle and fat).
   2. Glycogen synthase activation: For Glucose storage in the liver.
   3. mTOR activation: Acts as a Metabolic hub for growth.
   4. Transcription factors: Regulation of Protein expression. [10]

Describe the signaling cascade of glucagon once it binds to its receptor. [11]

Glucagon binds its receptor ( \rightarrow ) activates G protein ( \rightarrow ) increases cAMP (cyclic AMP) ( \rightarrow ) activates PKA (Protein Kinase A). [11]

What are the downstream effects of PKA activation in the glucagon pathway? [11]

1. Activation of Glycogen phosphorylase (leads to Glucose release).
   2. Stimulation of Gluconeogenesis (leads to Glucose production).
   3. Activation of mTOR and various Transcription factors. [11]

Why is there a "red circle with a cross" over the muscle in the glucagon action slide? [11]

Because Glucagon receptors are primarily located in the liver; glucagon does not trigger glycogen breakdown in skeletal muscle (muscle lacks the receptor for glucagon). [11]

How do Adrenaline and Cortisol differ in their roles during exercise vs. stress? [12]

Exercise primarily triggers Adrenaline, which promotes Glycogenolysis in muscle and liver.
Stress triggers both Adrenaline and Cortisol, which promote both Glycogenolysis and Gluconeogenesis (making new sugar for the "fight or flight" response). [12]

What is Proglucagon and where is it processed into different hormones? [13]

Proglucagon is a single precursor peptide. In Alpha cells, it is processed into Glucagon. In the gut (L-cells), it is processed into GLP-1 and GLP-2. [13]

What are the three primary roles of GLP-1 (Glucagon-like peptide-1) in glucose regulation? [14]

1. Stimulates Insulin release from Beta cells.
   2. Stimulates Somatostatin release from Delta cells (which then inhibits Glucagon).
   3. Directly inhibits Glucagon release from Alpha cells. [14]

How does the body sense changes in glucose levels at the cellular level? [15]

Through the metabolism of glucose to ATP, which regulates ion channels (like ( \text{K}_{\text{ATP}} )) and subsequent hormone release. [15]

Give an example of a therapeutic intervention targeting the pathways discussed in the lecture. [15]

GLP-1 agonists (e.g., Liraglutide, Semaglutide) are used to treat diabetes by mimicking the gut's natural signal to increase insulin and suppress glucagon. [15]

How does dysregulation of the glucose homeostasis system lead to disease? [15]

Constant high glucose or signaling errors can lead to insulin resistance, where cells no longer respond effectively to insulin signals, eventually resulting in Type 2 Diabetes. [15]