PHYS - Endocrine Pancreas

Question 1

What are Beta cells?

Answer 1

Beta cells are insulin and C peptide secreting cells found in the islets of langerhans of the pancreas

Beta cells make up 60-65% of the islet

Beta cells are typically found in the center of the islet

Question 2

What are alpha cells?

Answer 2

Alpha cells are glucagon secreting cells found in the islets of langerhans of the pancreas

Alpha cells make up 20% of the islet

Alpha cells are typically found at the periphery of islet

Question 3

What are delta cells?

Answer 3

Delta cells are somatostatin secreting cells found in the islets of langerhans of the pancreas

Delta cells make up 5% of the islet

Delta cells are typically located between the alpha and beta cells

Appear like neurons, have dendrite-like appendages that extend to beta cells

Question 4

How does paracrine signaling work in the islets of langerhans?

Answer 4

Beta cells secrete insulin, which inhibits glucagon secretion from alpha cells

Glucagon secretion from alpha cells promotes insulin secretion from beta cells

Somatstatin secretion from delta cells inhibits both insulin and glucagon secretion from beta and alpha cells, respectively

Question 5

Describe the process involved in secretion of insulin from pancreatic beta cells

Answer 5

Glucose enters the beta cell through the GLUT 2 transporter

Glucose is metabolized, causing an increase in intracellular ATP

Increased ATP causes ATP-dependent K+ inward rectifier channels to close.

With the channel closed, the cell membrane depolarizes, causing voltage-gated Ca2+ channels to open

Ca2+ floods into the cell increasing intracellular [Ca2+]

Increased [Ca2+] signals the exocytosis of insulin and C peptide

Question 6

What is sulfonylurea?

Answer 6

Sulfonylurea is a drug that blocks the ATP-Dependent K+ Inward Rectifier channel

By blocking this channel, insulin secretion is promoted

This drug is used to treat Type 2 Diabetes

Question 7

What are the two pathways of insulin signaling and what do they do?

Answer 7

Ras-Dependent Pathway - Growth effects

Ras-independent Pathway - Metabolic Effects (GLUT transporters, protease activity)

Question 8

How does Ras-Dependent Signaling occur?

Answer 8

Insulin binds to Receptor Tyrosine Kinase, causing dimerization and autophosphorylation of tyrosine kinase domains

Tyrosine Kinase phosphorylates IRS protein

Activated IRS protein then activates SHC, which activates GRB/SOS

GRB/SOS is responsible for Converting the GDP-bound RAS molecule into a GTP-bound RAS molecule

GTP-RAS then activates MAP Kinase which helps carryout growth effects

Question 9

How does the RAS-independent pathway work?

Answer 9

Insulin binds to Receptor Tyrosine Kinase causing dimerization and autophosphorylation of tyorsine kinase domains

Tyrosine kinase phosphorylates PI3 Kinase

PI3 Kinase converts PIP2 into PIP3

PIP3 activates PKB

PKB phosphorylates target proteins that cause various metabolic effects including translocation of GLUT transporters and activation of proteases

Question 10

What are the effects of insulin on skeletal muscle?

Answer 10

• Increase glucose uptake (GLUT 4)
• Increase glycogen synthesis
• Increase glycolysis and carbohydrate oxidation
• Decrease gluconeogenesis
• Increase protein synthesis
• Decrease protein breakdown

Question 11

How does glucose uptake occur in skeletal muscle without insulin signaling?

Answer 11

Contraction of skeletal muscle causes ATP to become AMP

AMP activates AMP Kinase

AMP Kinase begins a secondary messenger cascade that results in the translocation of GLUT4 transporters to the cell membrane

Highlights the importance of exercise with management of diabetes/insulin resistance

Question 12

What are the effects of insulin on adipocytes?

Answer 12

Overall insulin promotes uptake and storage of lipids

Insulin inhibits Hormone sensitive lipase activity (which promotes the breakdown of triglycerides into fatty acids)

Insulin promotes the uptake of glucose

Insulin promotes uptake of triglycerides via lipoprotein lipase

Insulin promotes uptake of fatty acids

Question 13

What stimulates insulin secretion?

Answer 13

Increased blood glucose
Increased blood amino acids
Increased blood fatty acids/ketoacids
Glucagon
Cortisol
Glucose-dependent Insulinotropic Peptide (GIP)
Vagal stimulation (ACh)
K+
Sulfonylurea drugs
Obesity

Question 14

What inhibits insulin secretion?

Answer 14

Decreased blood glucose
Somatostatin
Fasting
Exercise
Alpha-adrenergic agonists
Diazoxide

Question 15

How does type 2 diabetes progress?

Answer 15

Initially, insulin functions normally

Sedentary lifestyle, poor diet, obesity cause beta cells to be overworked, initially causing pancreatic beta cell hypertrophy

Insulin receptors become less sensitive insulin secretion, causing beta cells to produce even more insulin

Eventually causes beta cell failure, resulting in insulin deficiency (diabetes mellitus)

Question 16

What are incretin hormones?

Answer 16

Incretin Hormones are intestine derived hormones that stimulate insulin secretion, inhibit glucagon secretion, and slow gastric emptying

They are GLP-1 and GIP

These hormones are secreted in response to GI glucose and fat

Question 17

What effect does Type 2 diabetes have on incretin hormones?

Answer 17

Type 2 Diabetes reduces the effect of incretins, reducing their influence on insulin secretion

Question 18

What is the major stimulatory factor for glucagon secretion?

Answer 18

Decreased blood glucose

Question 19

What stimulates Glucagon secretion?

Answer 19

Fasting
CCK
Beta adrenergic agonists
ACh
Increased Amino Acids (arginine and alanine)

Question 20

What inhibits glucagon secretion?

Answer 20

Insulin
Somatostatin
Increased Fatty acids/ketoacid concentration

Question 21

What are the actions of glucagon?

Answer 21

Increases blood glucose
Increases glycogenolysis
Decreases glycogen synthesis
Increases gluconeogenesis

Directs metabolic pathways toward glucose formation

Also increases blood fatty acids/ketoacids by promoting lipolysis and inhibiting Fatty acid synthesis