Endocrine Pancreas Physiology + Blood Glucose Homeostasis

Question 1

How many cell types make up the endocrine pancreas? What percentage of the islet of Langerhaans is made up by each type?

Answer 1

• beta cells: insulin (65%)
• alpha cells: glucagon (20%)
• delta cells: somatostatin (10%)
• pancreatic polypeptide cells (5%)

Question 2

The gene for insulin is found on what chromosome? What type of hormone is it? What does this mean for its synthesis pathway?

Answer 2

• chromosome 11
• insulin is a peptide hormone (derived from amino acids)
• all peptide hormones are made from mRNA and ribosomal synthesis into a preprohormone (contains the hormone + a signal peptide + a connecting C peptide); the signal peptide is cleaved at the ER, forming the prohormone, which is packaged into secretory vesicles at the Golgi where the connecting peptide is cleaved, forming the hormone

Question 3

What is insulin’s structure?

Answer 3

• a peptide hormone with 2 straight chains (an alpha and beta chain) connected by 2 disulfide bridges
• there is a 3rd disulfide bridge within the alpha chain

Question 4

What is the major regulator of insulin synthesis and secretion?

Answer 4

• blood glucose levels

- (high glucose levels = more insulin)

Question 5

Explain how glucose stimulates insulin secretion.

Answer 5

• 1) glucose enters the beta pancreatic cells via GLUT-2 and undergoes glycolysis, which results in ATP generation
• 2) ATP causes ATP-dependent K+ channels to close, resulting in depolarization of the cell membrane
• 3) depolarization causes voltage-gated Ca2+ channels to open, and the increase in intracellular Ca2+ triggers insulin secretion via exocytosis of the secretory granules

Question 6

Why is insulin released faster with oral intake of glucose vs IV glucose?

Answer 6

• because the oral intake of glucose triggers the release of GIP (glucose-dependent insulinotropic peptide), which results in insulin secretion before the glucose is even digested (insulin is secreted in anticipation of the meal)

Question 7

Describe the structure of an insulin receptor and how the insulin-insulin receptor complex works.

Answer 7

• insulin receptors are tetramers made up of 2 alpha subunits and 2 beta subunits
• the alpha subunits contain the binding domain and the beta subunits have tyrosine kinase activity
• when insulin binds to the receptor, it induces a conformational change, resulting in autophosphorylation
• the activated tyrosine kinase then phosphorylates second messengers to instigate the proper response

Question 8

What’s insulin’s main purpose?

Answer 8

• to regulate blood glucose levels by storing excess nutrients as glycogen in the liver, as fat in adipose tissue, and as protein in muscle

Question 9

How does insulin decrease blood glucose levels? Blood fatty acid and ketoacid levels? Blood amino acid levels?

Answer 9

• decreases blood glucose by promoting its uptake by inserting GLUT-4 into fat and muscle cells; also by promoting glycogenesis and inhibiting gluconeogenesis
• decreases blood fatty acids by increasing their deposition in adipose tissue and inhibiting lipolysis (no free fatty acids also means no way to form ketoacids)
• decreases blood amino acids by increasing their uptake into cells; this results in increased protein synthesis, so insulin has an anabolic effect on protein

Question 10

When is glucagon secreted? What is its major function?

Answer 10

• glucagon is secreted during times of low blood glucose

- it promotes the mobilization and utilization of metabolic fuels to increase blood glucose levels

Question 11

Which organs does glucagon mainly affect? What actions does it trigger?

Answer 11

• major actions are on the liver
• increases glycogenolysis, gluconeogenesis, and lipolysis
• decreases glycogenesis, glycolysis, and fatty acid synthesis

Question 12

What role does pancreatic somatostatin play?

Answer 12

• it inhibits the secretion of both glucagon and insulin via paracrine action

Question 13

Which organs/cells rely solely on glucose for energy?

Answer 13

• RBCs, the nervous system, and the retina

Question 14

What are three mechanisms to decrease blood glucose? Four mechanisms to increase it?

Answer 14

• decrease BGL: increase insulin, increase parasympathetic activity, increase GIT hormones (GIP)
• increase BGL: increase glucagon, increase adrenaline, increase ACTH/cortisol, increase sympathetic activity