GW BGZ 2024 Case 2 - Postprandial transport and storage of nutrients

What happens after you eat a meal?

The fed state begins immediately after ingestion of a meal and typically lasts 3–5 hours. The primary goal is nutrient storage and synthesis. Key features include high insulin, low glucagon, active anabolic pathways, and coordinated organ-specific responses.

How is glucose absorbed and transported into tissues?

Intestinal absorption:

• SGLT1: Na⁺-dependent glucose/galactose cotransporter → apical enterocyte uptake

• GLUT5: Fructose transporter → apical membrane

• GLUT2: Basolateral membrane → monosaccharide exit to portal vein

Tissue-specific transporters:

• Liver: GLUT2 (insulin-independent, high capacity) → glycogen/fat synthesis

• Muscle & adipose: GLUT4 (insulin-dependent) → glycogen/triglyceride synthesis

• Brain: GLUT1 & GLUT3 (insulin-independent) → ATP production

• RBCs: GLUT1 → glycolysis

How does insulin regulate carbohydrate and fat metabolism in the fed state?

Source: Pancreatic β-cells
Stimulus: High glucose, amino acids, incretins (GLP-1, GIP)

Effects:

Glucose metabolism:

• ↑ GLUT4 translocation → glucose uptake

• ↑ Glycogenesis (liver/muscle)

• ↓ Glycogenolysis & gluconeogenesis

Lipid metabolism:

• ↑ Lipogenesis in liver/adipose

• ↑ LPL → FFA uptake into adipose

• ↓ Hormone-sensitive lipase → decreased lipolysis

Protein metabolism:

• ↑ Amino acid uptake

• ↑ Protein synthesis

• ↓ Protein breakdown

Net effect: Promotes energy storage and anabolic metabolism

What are the fates of glucose in the fed state?

1. Energy Production

Glucose → Glycolysis → Pyruvate

If oxygen present:

• Pyruvate → Acetyl-CoA → Citric Acid Cycle → Electron Transport Chain → ATP

If no mitochondria (RBCs):

• Pyruvate → Lactate

2. Storage Pathways

A. Glycogenesis (Short-Term Storage)

Glucose → Glucose-6-phosphate → Glycogen

• Liver glycogen (50-80 grams)

  • Maintains blood glucose between meals

  • Approx. 4-hour supply

• Muscle glycogen (350-800 gram)

  • Used locally for contraction

  • Cannot be exported (muscle lacks glucose-6-phosphatase)

B. Lipogenesis (Long-Term Storage)

When glycogen stores are full:

• Excess glucose → Acetyl-CoA

• Acetyl-CoA → Fatty acids

• Fatty acids + glycerol → Triglycerides

• Stored in adipose tissue

This process requires insulin.

How is glucose handled postprandially in different tissues?

Tissue	Transporter	Fate
Liver	GLUT2	Glycogen synthesis, de novo lipogenesis
Muscle	GLUT4	Glycogen synthesis, ATP production
Adipose	GLUT4	Glycerol-3-phosphate → triglyceride synthesis
Brain	GLUT1 & GLUT3	ATP production (insulin-independent)
RBC	GLUT1	Glycolysis → lactate (Cori cycle)

What is the normal fasting blood glucose concentration?

The normal fasting blood glucose concentration is approximately 5.0 mmol/L.

• The body tightly regulates blood glucose to prevent hyperglycemia, which can damage blood vessels, and hypoglycemia, which can impair brain function.

• After ingestion of a sugary drink (e.g., a glass of Coke), blood glucose rises modestly, because insulin and other regulatory mechanisms prevent dangerous spikes.

What is the role of the pancreas in glucose metabolism?

The pancreas regulates blood glucose via insulin and glucagon.

• Insulin: Produced by β-cells in the islets of Langerhans.

  • Stimulated by high blood glucose.

  • Promotes glucose uptake and storage (liver, muscle, adipose).

  • Excessive blood glucose without insulin → vascular damage.

• Glucagon: Produced by α-cells.

  • Stimulated by low blood glucose.

  • Promotes glycogen breakdown and gluconeogenesis in the liver.

  • Insufficient glucagon → hypoglycemia, loss of consciousness, brain energy deficit.

• Overall role: Maintain homeostasis, keeping glucose within a narrow physiological range, using hormones to coordinate liver, muscle, and adipose tissue metabolism.

What is the role of the liver in glucose metabolism?

The liver is the primary organ that maintains blood glucose.

Fed state (high glucose, high insulin):

• Glucose enters hepatocytes via GLUT2 (insulin-independent).

• Glucose → glucose-6-phosphate → glycogen (via glycogen synthase, activated by insulin).

• Glycogen storage avoids osmotic stress, because storing free glucose would draw water into cells.

Fasted state (low glucose, low insulin, high glucagon/adrenaline):

• Glycogen breakdown (glycogen phosphorylase activation) → glucose release into blood.

• Glucose-6-phosphate can also enter glycolysis or citric acid cycle for energy.

Summary:

• Prevents hypoglycemia

• Stores glucose as glycogen in fed state

• Releases glucose in fasting/overnight periods

• Supports insulin-independent tissues (brain, RBCs, active muscle)

Why is glycogen stored in the liver rather than free glucose?

Glycogen is a polysaccharide polymer of glucose:

• Reduces osmotic pressure: storing many glucose molecules as one glycogen particle prevents water influx.

• Provides a compact, energy-dense storage form for rapid mobilization.

• Liver glycogen ranges 70–100 g, varying by time of day and fasting duration (morning levels lower due to nocturnal usage).

How does skeletal muscle handle glucose?

• Muscle glycogen stores: 350–800 g, varying with activity and fed/fasted state.

• Glucose uptake: insulin-dependent via GLUT4.

  • During contraction: Ca²⁺ and AMPK activation allow insulin-independent uptake.

• Glycogen breakdown is stimulated by adrenaline and contraction.

• Muscle lacks glucose-6-phosphatase, so glucose cannot be released into the blood.

• High Pi and AMP indicate ATP consumption → glycogenolysis for energy.

Compare glucose handling in the liver vs skeletal muscle.

Feature	Liver	Skeletal Muscle
Glucose uptake	Insulin-independent (GLUT2)	Insulin-dependent (GLUT4)
Glycogen use	Can release glucose into blood	Cannot release glucose; used internally
Glycogen synthase	Activated by insulin	Activated by insulin
Glycogen phosphorylase	Activated by glucagon/adrenaline	Activated by adrenaline/contraction
Function	Maintains blood glucose	Supplies energy for contraction
Max glycogen	70–100 g	350–800 g

What is the role of adipose tissue in carbohydrate metabolism?

Adipose tissue converts glucose into triglycerides for long-term energy storage:

Fed state (high glucose, high insulin):

• Glucose uptake via GLUT4 (insulin-dependent).

• Glucose → glycerol-3-phosphate → backbone for triglycerides.

• Supports lipogenesis and fat storage.

Fasted state (low glucose, low insulin):

• Lipolysis activated → fatty acids and glycerol released into blood for energy by other tissues.

Additional points:

• The TCA (Krebs) cycle provides intermediates for fat synthesis.

• Adipose works in coordination with liver and muscle to manage energy storage and supply.

How does glycogenesis in the liver work during a fed state vs fasted state?

• Green arrow: when you eat a meal

  • Insulin stimulates glycogen synthase → glycogen can be produced

• Green is stimulation

• Red is inhibition

How does glycogenesis in skeletal muscle work during a fed state vs fasted state?

• Similar conversions and enzymes

• 350–800g glycogen

  • A bigger range

  • Depends on the condition: fasted or fed, exercise

Summary: role of the liver in carbohydrate metabolism

• High blood glucose > high insulin

• Glucose uptake by liver (insulin-independent) and storage as glycogen (insulin activates glycogen synthase)

  • GLUT2 receptor is glucose independent → glucose can always enter the liver

• Inhibition of glycogen breakdown by insulin

• Low blood glucose > low insulin

• Breakdown of glycogen and release of glucose by the liver into the blood (glucagon and (nor)adrenaline activate glycogen phosphorylase)

• Utilisation of blood glucose by tissues with insulin-independent glucose uptake (brain, red blood cells, active muscle)

Summary: role of muscle in carbohydrate metabolism

• High blood glucose > high insulin

• Glucose uptake by muscle (insulin-dependent) and storage as glycogen (insulin activates hexokinase and glycogen synthase)

• Inhibition of glycogen breakdown by insulin

• Low blood glucose > low insulin

• Breakdown of glycogen and oxidation of glucose by the muscle (adrenaline and contraction activate glycogen phosphorylase)

• No release of glucose into the blood

• Insulin-independent glucose uptake in active muscle via AMPK

  • The muscles contracts

  • AMPK → glucose can enter the cell without insulin

What is the role of adipose tissue in glucose metabolism?

• High blood glucose > high insulin

• Glucose uptake by adipocytes (insulin-dependent)

• Used for fat storage

• Low blood glucose > low insulin

• Breakdown of fat and release of fatty acids and glycerol into the blood

What is an apolipoprotein and what are its functions?

An apolipoprotein is the protein component of a lipoprotein particle. Its major functions are:

1. Structural role: Stabilizes the lipoprotein particle in the aqueous environment of plasma.

2. Enzyme cofactor: Activates or inhibits enzymes involved in lipid metabolism (e.g., ApoC-II activates lipoprotein lipase).

3. Ligand for receptors: Mediates cellular uptake of lipoproteins by interacting with specific receptors (e.g., ApoE binds to hepatic LDL receptors).

Apolipoproteins are essential for lipid transport, metabolism, and clearance, connecting dietary and endogenous fat pathways.

What are nascent chylomicrons, and what are their components?

Nascent chylomicrons are newly formed triglyceride-rich lipoproteins secreted by enterocytes in the small intestine after a meal.

• Components and approximate proportions:

Component	Function	Proportion
Triglycerides (TAG)	Main energy cargo; reassembled from fatty acids + monoglycerides	~85%
Cholesterol (free + esterified)	Structural role and transport	~3–5%
Phospholipids	Surface layer to solubilize hydrophobic core	~7–10%
ApoB-48	Structural protein, essential for chylomicron assembly	1 copy per particle
Fat-soluble vitamins (A, D, E, K)	Transport in circulation	Trace

• ApoB-48: synthesized in intestinal cells, required for chylomicron formation, cannot bind LDL receptors.

• Nascent chylomicrons are secreted into the lymph, entering the bloodstream via the thoracic duct.

How do nascent chylomicrons convert to mature chylomicrons?

In the bloodstream, nascent chylomicrons acquire apolipoproteins from HDL:

1. ApoC-II → Activates lipoprotein lipase (LPL) for triglyceride hydrolysis into free fatty acids (FFA) and glycerol.

2. ApoE → Mediates hepatic uptake of chylomicron remnants.

Once they acquire these, they are called mature chylomicrons, capable of delivering dietary triglycerides to adipose, skeletal muscle, and cardiac muscle.

Which organs and enzymes are involved in chylomicron triglyceride metabolism?

Organs (capillary endothelium):

• Adipose tissue → stores fatty acids as triglycerides

• Skeletal muscle → oxidizes fatty acids for energy

• Cardiac muscle → preferentially oxidizes fatty acids

Enzyme:

• Lipoprotein lipase (LPL), activated by ApoC-II, hydrolyzes triglycerides → FFA + glycerol.

• Fate of products:

  • FFA → taken up by tissues for storage (adipose) or energy (muscle/heart)

  • Glycerol → transported to liver for gluconeogenesis or triglyceride synthesis

What are chylomicron remnants, and how are they processed?

Chylomicron remnants are particles remaining after LPL has removed most triglycerides.

Features:

• Smaller in size

• Triglyceride content reduced (~1:1 with other lipids)

• ApoC returned to HDL

• Retains ApoB-48, ApoE, and cholesterol-rich core

Liver uptake:

• ApoE binds to hepatic receptors (LDL receptor, LDL receptor–related protein) → endocytosis into hepatocytes

• Liver processes remnants:

  • Releases cholesterol → bile acid synthesis or VLDL assembly

  • Releases triglycerides

  • Recycles apolipoproteins

Connection to other lipoproteins: Lipid from remnants is incorporated into VLDL, linking dietary fat to endogenous lipid transport (IDL → LDL).

How is VLDL synthesized and secreted by the liver?

VLDL (Very Low-Density Lipoprotein):

1. Triglyceride synthesis: Fatty acids + glycerol → TAG in smooth ER

2. Lipoprotein assembly: TAG + cholesterol + phospholipids + ApoB-100

   • ApoB-100 is the structural protein

   • Assisted by microsomal triglyceride transfer protein (MTP)

3. Maturation and secretion: Nascent VLDL transported through Golgi → mature VLDL → bloodstream

Fate in circulation:

• Acquires ApoC-II and ApoE from HDL

• LPL hydrolyzes triglycerides → VLDL shrinks → IDL → LDL

• APO B-100 instead of APO B-40

• Ratio 5:1 instead of 10:1

• VLDL obtains APO C-2 and ratio stays the same

• Remant: where lipids have been cleaved off

• There is a recycling of lipids

• LDL goes back to the liver

• Cholesterol from the LDL can be used by some cells

What is the composition and function of LDL?

LDL (Low-Density Lipoprotein):

Component	Function
Cholesterol-rich core	Delivers cholesterol to tissues
Triglycerides	Minimal remaining from VLDL conversion
ApoB-100	Structural protein; ligand for LDL receptor
Phospholipids	Solubilizes lipids

Key points:

• Delivers cholesterol to tissues

• Some LDL not cleared efficiently → oxidation → taken up by macrophages → foam cell formation → atherosclerosis

• Considered “bad” because excess LDL → plaque formation in arteries → cardiovascular disease

What is HDL and its role in reverse cholesterol transport?

HDL (High-Density Lipoprotein):

• Synthesized in liver and intestine

• High protein content (dense)

• Contains ApoA-I and other apolipoproteins

• Small cholesterol/triglyceride content

Functions:

1. Collects excess cholesterol from peripheral tissues/foam cells → liver

2. Esterifies cholesterol via LCAT

3. Donates ApoC and ApoE to chylomicrons/VLDL

4. Antioxidant/anti-inflammatory → protects LDL from oxidation

Clinical significance:

• Higher HDL → reduced atherosclerosis risk

• “Good cholesterol” due to removal of cholesterol from plasma and prevention of LDL oxidation

What is the fate of dietary triglycerides in the fed state?

• Absorbed as FFA + monoacylglycerol → re-esterified in enterocytes → chylomicrons

• Chylomicrons transport TAG → muscle/adipose

• LPL hydrolysis: TAG → FFA + glycerol

• FFA → energy (muscle) or storage (adipose)

• Glycerol → liver → gluconeogenesis or TAG synthesis

• Chylomicron remnants → liver → recycled → VLDL synthesis

What is the exogenous pathway of fat metabolism?

1. Chylomicrons formed in intestine → enter lymphatics → circulation.

2. Acquire ApoC-II from HDL, which activates lipoprotein lipase (LPL).

3. LPL hydrolyzes TAG → FFA taken up by adipose or muscle.

4. Chylomicron remnants (with ApoE, ApoB-48) are taken up by the liver.

Key roles of apolipoproteins:

• ApoC-II → LPL activator

• ApoE & ApoB-48 → liver receptor ligands

How does lipogenensis work? (when you eat)

How does lipolysis work? (fasted state)

Remember the names in red and the enzymes and hormones. It is important you understand it and it is logic → less learning

Summary: role of adipose tissue in fat metabolism

• Chylomicrons high

• High blood glucose > high insulin

• LPL stimulation

• Uptake of FFA by adipocytes and storage as fat

• Inhibition of fat breakdown by insulin

• Low blood glucose > low insulin

• High (nor)adrenaline

• Breakdown of fat and release of FFA into the blood

What is the role of the liver in fat metabolism?

• Same transport proteins and conversion steps

• Lipids can be stored in the liver

• Liver can only make VLDL from TAG

• No LPL but hepatic lipase

• No GLUT4, but GLUT2

What is the endogenous fat pathway?

1. Liver produces VLDL with TAG from de novo lipogenesis or stored fat.

2. VLDL enters circulation → acquires ApoC-II from HDL → substrate for LPL.

3. TAG hydrolyzed → FFA uptake by adipose and muscle.

4. VLDL remnant → converted to LDL → recycled to liver or used for cholesterol in tissues.

Differences with chylomicrons:

• ApoB-100 instead of ApoB-48

• Lower TAG:protein ratio (≈5:1 vs 10:1)

What is the role of skeletal muscle in fat metabolism?

• During exercise, FFA oxidation is critical for energy.

• Stimulated by:

  • Adrenaline (β-adrenergic)

  • Calcium signaling (muscle contraction)

• Provides ATP for sustained muscle activity.

What is de novo lipogenesis and when does it occur?

• De novo lipogenesis: synthesis of fatty acids from non-lipid precursors (glucose, fructose, amino acids → acetyl-CoA).

• Occurs mainly in liver and adipose tissue.

• Stimulated by high insulin (fed state).

• Excess carbohydrate → stored as fat.

How are carbohydrate and fat metabolism integrated?

• Fed state: high glucose → high insulin →

  • Glucose stored as glycogen or converted to fat (de novo lipogenesis).

  • TAG stored in adipose tissue via LPL.

• Fasted state: low glucose → low insulin, high glucagon/adrenaline →

  • Glycogen breakdown → glucose for brain and RBCs.

  • Lipolysis → FFA for muscle and liver oxidation.

  • Gluconeogenesis → maintains blood glucose.

• Exercise:

  • Muscle uses glucose and FFA.

  • AMPK and calcium allow insulin-independent uptake of glucose.

  • Adrenaline stimulates glycogenolysis and FFA release.

Key principle: Metabolic pathways operate selectively depending on hormonal/nutritional status.

Overall summary: fasted state (postabsorptive)

• Glucose and insulin low, glucagon high

• Production of glucose by breakdown of liver glycogen (glycogenolysis) and gluconeogenesis

• Glucose uptake by brain, red blood cells

• Fat tissue produces free fatty acids and glycerol (lipolysis)

• Skeletal muscle oxidizes mainly free fatty acids (glucose oxidation is relatively low)

• Liver oxidizes rather than re-esterifies FA (low insulin/glucagon ratio); ATP used for gluconeogenesis; production of ketone bodies

Overall summary: after meal intake (postprandial)

• Mixed meal consisting of CHO, fat and protein

• Absorption glucose within 15-30 minutes

• Insulin increases, glucagon decreases

• Liver: uptake of glucose (insulin independent via GLUT2), stimulation of glycogen synthesis (glycogenesis) (high ratio insulin/glucagon)

• Muscle: glucose uptake (insulin-dependent via GLUT4), glycogen synthesis and glucose oxidation; inhibition of fatty acid oxidation via malonyl-CoA

• Adipose tissue: uptake of glucose (used for fat storage), inhibition of lipolysis.

• After ~4 hours, chylomicrons appear in the blood

• LPL activity in adipose tissue capillaries stimulated by insulin

• LPL breaks down TAG from chylomicrons

• Adipose tissue takes up fatty acids and turns them into fat

What defines the fasted state and when does it begin?

• Begins approximately 4–6 hours after a meal, when plasma glucose from nutrient absorption falls.

• The body shifts from the fed (anabolic) state to the fasted (catabolic) state.

• Key goals:

  • Maintain blood glucose for glucose-dependent tissues (brain, RBCs).

  • Mobilize stored energy from glycogen, fat, and protein.

  • Switch to catabolic metabolism to provide ATP while sparing glucose.

• Controlled by hormones (insulin decreases; glucagon, epinephrine, cortisol, GH increase).

• Catabolic pathways: glycogenolysis, gluconeogenesis, lipolysis, proteolysis.

• Proteins and fats are mobilized to spare plasma glucose for the brain and red blood cells.

How is glucose regulated during early fasting (4–12 hours)?

• Primary source: liver glycogen.

• Liver glycogenolysis: glycogen → glucose-1-phosphate → glucose-6-phosphate → free glucose.

• Glucose exits hepatocytes via GLUT2 (insulin-independent).

• Plasma glucose maintained within a narrow physiological range.

• Muscle glycogen is not used to maintain blood glucose; it is used locally for energy.

• Peripheral tissues (muscle, adipose) reduce glucose uptake by internalizing GLUT4 transporters, shifting to fatty acid oxidation.

• Ensures glucose is spared for brain and RBCs.

Define glycogenolysis and its role in fasting.

• Glycogenolysis: breakdown of glycogen into glucose or glucose-6-phosphate.

• Purpose: maintain plasma glucose, especially during early fasting (post-absorptive state).

• Key steps:

  1. Glycogen phosphorylase: removes glucose units as G1P. Activated by glucagon/epinephrine, inhibited by insulin.

  2. Debranching enzyme: handles α-1,6 branch points; releases free glucose.

  3. Phosphoglucomutase: converts G1P → G6P.

  4. Glucose-6-phosphatase: in liver converts G6P → free glucose → blood.

• Muscle glycogen: lacks glucose-6-phosphatase → glucose-6-phosphate used internally for ATP (glycolysis), lactate exported for gluconeogenesis (Cori cycle).

What is gluconeogenesis and what is it’s role in fasting?

• Activated after glycogen stores are depleted

  • Starts roughly 4 hours after a meal

  • Increases during prolonged fasting or starvation

• Purpose: maintain blood glucose for the brain, RBCs, and other glucose-dependent tissues

1. Substrate entry

   • Lactate → pyruvate (via lactate dehydrogenase)

   • Glycerol → DHAP

   • Alanine → pyruvate (via alanine transaminase)

2. Reversal of glycolysis

   • Most glycolytic steps reversed

   • Three irreversible glycolysis steps bypassed using specific enzymes:

     • Pyruvate → oxaloacetate → phosphoenolpyruvate (PEP)

     • Fructose-1,6-bisphosphate → fructose-6-phosphate

     • Glucose-6-phosphate → glucose

3. Glucose output

   • Glucose-6-phosphate → free glucose via glucose-6-phosphatase (liver, kidney)

   • Released into bloodstream

How does prolonged fasting (>12–24 h) affect glucose metabolism?

• Liver glycogen stores largely depleted.

• Blood glucose maintained primarily via gluconeogenesis.

• Sites of gluconeogenesis:

  • Liver → main site.

  • Kidney cortex → contributes during prolonged fasting.

• Substrates:

  • Lactate: from RBCs and anaerobic muscle; Cori cycle.

  • Glycerol: from adipose triglyceride breakdown; converted to DHAP → glucose.

  • Amino acids: alanine from muscle proteolysis; glutamine for kidney gluconeogenesis.

• Mechanism:

  1. Substrate entry (lactate → pyruvate; glycerol → DHAP; alanine → pyruvate).

  2. Reversal of glycolysis using specific bypass enzymes: pyruvate → PEP, F1,6BP → F6P, G6P → glucose.

  3. Glucose-6-phosphate → free glucose via glucose-6-phosphatase → bloodstream.

• Brain still requires glucose; RBCs rely entirely on glycolysis.

How is skeletal muscle glycogen utilized?

• Glycogen → Glucose-6-phosphate → Glycolysis.

• Products depend on oxygen availability:

  • Aerobic: Glucose-6-phosphate → pyruvate → enters mitochondria → TCA cycle → ATP.

  • Anaerobic: Glucose-6-phosphate → pyruvate → lactate.

• Lactate and pyruvate are transported to the liver for gluconeogenesis.

What is the Cori cycle?

• The Cori cycle is the process where lactate produced by skeletal muscle during anaerobic glycolysis is transported to the liver, converted back into glucose via gluconeogenesis, and released into the bloodstream.

• Steps:

  1. Muscle glycogen → G6P → pyruvate → lactate (anaerobic).

  2. Lactate enters liver via bloodstream.

  3. Liver converts lactate → pyruvate → glucose via gluconeogenesis.

  4. Glucose released into plasma → available for muscle and other tissues.

• Purpose: allows muscles to generate ATP anaerobically while still maintaining blood glucose levels indirectly.

How is lipid metabolism affected in the fasted state?

• Primary energy storage: triglycerides in adipose tissue.

• Lipolysis triggers: low insulin, high glucagon, high epinephrine → activate hormone-sensitive lipase (HSL).

• Triglycerides → glycerol + 3 fatty acids:

  • Glycerol: transported to liver → converted to glycerol-3-phosphate → gluconeogenesis → glucose.

  • Fatty acids: bound to albumin → transported to liver and muscle → beta-oxidation → acetyl-CoA → TCA cycle → ATP.

• Ketone body formation:

  • Excess acetyl-CoA → converted to ketone bodies (acetoacetate, β-hydroxybutyrate, acetone).

  • Ketones provide alternative brain fuel during prolonged fasting.

Which hormones regulate fasting metabolism?

Hormone	Source	Fasted State Role
Insulin	Pancreatic β-cells	Low levels → ↓ glucose uptake (muscle/adipose), ↓ glycogenesis/lipogenesis, disinhibits HSL and gluconeogenesis.
Glucagon	Pancreatic α-cells	Elevated → ↑ glycogenolysis, ↑ gluconeogenesis, ↑ lipolysis.
Epinephrine	Adrenal medulla	↑ glycogenolysis (liver/muscle), ↑ lipolysis (adipose), stimulates Cori cycle.
Cortisol	Adrenal cortex	↑ proteolysis → amino acids for gluconeogenesis, permissive lipolysis, reduces peripheral glucose uptake.
Growth Hormone	Anterior pituitary	↑ lipolysis, ↓ glucose uptake in muscle/fat, preserves protein, promotes fatty acid utilization.

How do transporters change in fasting?

Tissue	Transporter	Role in Fasting
Liver	GLUT2	Insulin-independent glucose release into blood.
Muscle	GLUT4	Internalized; glucose uptake decreases.
Adipose	GLUT4	Internalized; glucose uptake decreases.
Brain	GLUT1 & GLUT3	Maintained glucose uptake.
FFA	FAT/CD36, albumin	Fatty acids transported to liver and muscle for oxidation.