Endocrine Pancreas

Question 1

Islets of Langerhans

Answer 1

Clusters of cells releasing insulin, glucagon and somatostatin

Question 2

What cells release glucagon, insulin, C peptide, pancreatic polypeptide and somatostatin

Answer 2

B-cells release insulin and C-peptide
alpha-cells release glucagon
D-cells release somatostatin
F cells secrete pancreatic polypeptide

Question 3

Steps of insulin release

Answer 3

Glucose enters cells via GLUT-2 transporter
Glucose phosphorylated by glucokinase
G6P is oxidized which promotes ATP generation
ATP closes inward rectifying K+ channels causing depolarization
VG-Ca channels activated which initiates mobilization of insulin and C-peptide and exocytosis results

Question 4

Sulfonylurea receptor

Answer 4

Associated with ATP-dependent K+ channels, increase insulin secretion

• causes membrane depolarization to occur more easily
• more Ca entry
• treats type II DM

Question 5

Insulin receptor

Answer 5

Bound- insulin receptor autophosphorylates itself and phosphorylates other proteins
Insulin-receptor complex is internalized by target cells
Downregulation of receptor by insulin itself
Causes translocation of vesicles containing GLUT4 to the membrane - allowing glucose to enter cells

Question 6

AMP Kinase

Answer 6

Activation of AMP-kinase results in GLUT4 translocation to plasma membrane
Muscle contractions stimulate this process
Therefor, doing insulin injections during exercise can cause a hypoglycemic state

Question 7

Insulin stimulating factors

Answer 7

Increased AA, FA
Glucagon
Cortisol
GIP
K+
Vagal stimulation
Sulfonylurea drugs

Question 8

Insulin inhibitory factors

Answer 8

Fasting
Exercise
Somatostatin
a-adrenergic agonists;norepinephrine
Diazoxide (K+ channel activator which relaxes smooth muscle)

Question 9

Gut hormones and insulin

Answer 9

Hormones such as CCK and GLP-1 that are secreted during meals help cause insulin release
If these pathways are effected, insulin release will be as well

Question 10

Secretion of glucagon

Answer 10

Insulin inhibits glucagon production and secretion
Glucagon increases blood glucose by inhibited glycogen synthesis and activation glycogenolysis
Stimulates lipolysis in adipose tissue and skeletal muscle

Question 11

Type I DM

Answer 11

Destruction of B-cells
Decreased utilization of ketoacids leads to diabetic ketoacidosis
Hyperkalemia (intracellular potassium is low, may or may not have high extracellular K+)
Osmotic diuresis/Glucosuria- polyurea

Question 12

Type II DM

Answer 12

Progressive exhaustion of B-cells due to environmental factors
Patients still produce insulin

Question 13

Progression of insulin resistance and type 2 DM

Answer 13

Reactive hyperinsulinemia
Obesity-induced insulin resistance: decreased GLUT4 uptake of glucose in response to insulin
Decreased ability of insulin to repress hepatic glucose production
Inability of insulin to repress adipose tissue uptake (via LPL) and lipolysis (via HSL) - fatty liver disease
Hyperglucagonemia

Question 14

Stages of glucose/insulin levels in type 2 DM

Answer 14

At first, glucose looks normal but insulin must be higher to take in the glucose
Then glucose in-between or after meals is elevated
Then fasting glucose levels are elevated
Eventually beta cells will die off and patient will present more like type I diabetic (in terms of insulin release)

Question 15

Treatment of type 2 DM

Answer 15

Insulin sensitizers like metformin
Slow absorption of CHO via a-glucosidase inhibitors or amylin analogs
Insulin secretagogues such as sulfonylurea drugs or analogs of GLP1