Physiology: Endocrine Pancreas Flashcards
(36 cards)
What are the cells of the pancreas and what do they secrete?
- Beta: insulin and amylin
- Alpha: glucagon
- Delta: somatostatin
What is the innervation of the Islets of the pancreas?
- Adrenergic nerves → via α2 receptors, inhibit insulin release
- Cholinergic nerves → via M3 receptors, promote insulin release
- Peptidergic neurons (e.g., GLP-1 from the gut) → also enhance insulin release
Why does IV glucose not cause as much insulin release as Oral glucose?
because oral glucose stimulates GLP-1 in the gut to release more insulin –> IV does not go through the gut
What is the composition of Insulin?
peptide hormone made of:
- A chain and B chain
- Connected by disulfide bonds
- third C chain (C peptide) connects them during early formation
What is C peptide used for?
Used clinically to measure natural insulin secretion in diabetics on insulin (because injected insulin doesn’t contain C peptide)
What is the most important factor controlling insulin release and how does it release insulin?
glucose
1) Glucose enters via GLUT2
2) Glucose is metabolized to generate ATP
3) ATP closes ATP-sensitive K+ channels
4) membrane depolarization and opening of voltage-gated Ca 2+ channels
5) Increase in intracellular Ca 2+ –> release of insulin granules
What other factors increase insulin secretion?
- increase in amino acids (ATP/ADP ratio)
- increase in fatty acids (ATP/ADP ratio)
- increase in glucagon (Ga-q pathway)
What are drugs that stimulate and inhibit insulin secretion?
- Diazoxide: opens K+ channels –> hyperpolarization –> inhibition
- Sulfonylurea: blocks ATP-K+ channels –> depolarization –> insulin release
Who is mainly prescribed Sulfonylurea drugs?
non-insulin dependent type II diabetics
How is insulin cleared from the body ?
Broken down in the liver and kidney by enzymes that break disulfide bonds
What is the signaling process of Insulin binding to its receptor?
1) Insulin binds to alpha subunits
2) causes a conformational change
3) Beta-subunits auto-phosphorylate each other (activates tyrosine kinase)
4) Activated tyrosine kinase phosphorylates other proteins like:
- IRS (Insulin Receptor Substrates)
- leads to activation/inhibition of downstream pathways
Explain the Insulin Receptor Down-Regulation process and what can occur?
- Receptor complex is internalized (endocytosis) when insulin levels are too high
- may be recycled or degraded
***If degraded: insulin downregulates its own receptor –> contributes to insulin resistance (as in Type II Diabetes)
Where is GLUT1 located, when is it active and what is its main function?
- Where: RBCs, brain endothelium, muscle, fat
- When: Always active
- Function: Basal glucose uptake
Where is GLUT2 located, when is it active and what is its main function?
- Where: Liver, pancreas (β-cells), kidney, intestine
- When: Only active when glucose is high
- Function: Senses glucose levels and regulates insulin release
Where is GLUT3 located, when is it active and what is its main function?
- Where: Neurons
- When: Always active
- Function: Glucose uptake in the brain (with GLUT1)
Where is GLUT4 located, when is it active and what is its main function?
- Where: Muscle and fat
- When: Insulin-dependent (stored in vesicles)
- Function: Main insulin-responsive glucose transporter
Where is GLUT5 located, when is it active and what is its main function?
- Where: Sperm and small intestine
- When: digestion of meal
- Function: Transports fructose, not glucose
What are the 6 actions of Insulin on peripheral tissues?
- ↓ Blood glucose via GLUT4
- ↑ Glycogen synthesis; ↓ glycogenolysis & gluconeogenesis
- ↑ Fat storage; ↓ lipolysis & ketoacids
- ↓ Blood amino acids (anabolic effect)
- ↑ K⁺ uptake (via Na⁺/K⁺ ATPase)
- ↓ Appetite; ↑ energy use (via hypothalamus)
What is the Pathophysiology of Type I diabetes?
an inability to make insulin (insulin-dependent diabetes mellitus)→ glucose cannot enter cells, so the body behaves as if it’s in a fasting state even when glucose is high
What are the metabolic consequences of Type I diabetes?
- ↓ Glucose utilization → leads to ↑ plasma glucose (hyperglycemia)
- ↑ Fat & protein utilization → to make ATP, the body breaks down fat (↑ FFAs) and muscle (↑ protein catabolism)
→ Results in ketoacidosis and muscle wasting
What are the renal and fluid consequences of Type I diabetes?
- glucose exceeds SGLT reabsorption → glucose enters urine → causes polyuria (osmotic diuresis)
- water is pulled from cells → triggers thirst → causes polydipsia
- continued water loss = ECF depletion → dehydration and hyperosmolarity → worsens uncontrolled Type I diabetes
What are the electrolyte shifts that occur with a lack of insulin?
- ↑ K⁺ in blood = hyperkalemia
- ↓ Na⁺ = due to osmotic shift of water and solutes → can lead to impaired neural reflexes and peripheral neuropathy
What are the Chronic Effects of Type I diabetes?
Persistent high glucose damages tissues:
- ↑ glycosylated proteins → stiffens blood vessels → hypertension
- ↑ risk of diabetic complications (e.g., kidney damage, nerve damage, cardiovascular issues)
What are the metabolic effects of excess FFAs due to the absence of insulin in diabetics?
- FFAs are converted into phospholipids and cholesterol in the liver which raises LDL-C levels, which increases risk for atherosclerosis in diabetics
