Physiology of Pancreas

Question 1

Which hormones are released during the fasting state?

Answer 1

• Glucagon
• Catecholamines
• Cortisol (supplementary if the first two don’t get the job done)
• Growth hormone (supplementary if the first two don’t get the job done)

Question 2

What are the sources of control of the synthesis and secretion of islet hormones?

Answer 2

• Humoral communication
  
  • ​Blood supply of the islet course otuward from the center toward the periphery, carrying glucose and other secretagogues
• Cell-cell communication
  
  • ​Cells within an islet connect with one another and communicate through gap junctions
• Neural communication
  
  • ​Islets are innervated by the sympathetic and parasympathetic divisions of the ANS

Question 3

Products of alpha cells

Answer 3

• Glucagon (20% of islet cells located near periphery)

Question 4

Products of beta cells

Answer 4

• Insulin-60-75% of islet cells located mainly in the center
• Amylin

Question 5

Products of delta cells

Answer 5

• Somatostatin- 5% of islet cells interspersed between the alpha and beta cells

Question 6

Products of F cells

Answer 6

Pancreatic polypeptide

Question 7

Insulin is encoded by a single gene on Chromosome ___.

Answer 7

11

Question 8

Insulin synthesis and secretion is stimulated when islets are exposed to glucose. What are the components of the secretory granules that secrete insulin?

Answer 8

Insulin, C peptide and a small amount of proinsulin

NOTE: The half-life of insulin is approximately 5 mins

Question 9

What are the mechanism by which insulin beinds to it’s cell receptors?

Answer 9

1. Insulin binds to specific receptor tyrosine kinase on the plasma membrane
2. Insulin recept can phosphorylate both itself and other intracellular substrate at tyrosine kinase residues
3. insulin is able to transmit its signal across the plasma membrane of insulin target tissues

Question 10

Approximately 60% of insulin that enters into the portal vein is removed by the _____.

Answer 10

Liver

NOTE: C-peptide is not extracted by the liver, but is excreted by the kidneys. This is important diagnostically. C-peptide is not harmed by the liver, so it makes it out of circulation in the exact amount that the beta cells synthesized it.

Question 11

High C-peptide levels are diagnostic of __________.

Answer 11

DM II

Question 12

When is glucose response to insulin maximal?

Answer 12

When only approximately 5% of the receptors are occupied

Question 13

What effect does insulin have at the liver?

Answer 13

Glycolysis

Glycogen synthesis

Liogenesis

Protein Metabolism

Question 14

The biggest issue with diabetes is the inability of ______ to take up glucose.

Answer 14

Skeletal muscle

Question 15

Function of insulin at skeletal muscle

Answer 15

• Increases GLUT4 translocation
• Increases glycogen synthesis
• Increase glycolysis
• Increases protein synthesis and slows protein degradation
• Increases triglycerides

Question 16

Function of insulin at adipocytes

Answer 16

• Increase GLUT4 transporters
• Increase glycolysis
  
  • Increase in a-glycerol phosphate
  • Increase in acteyl CoA
  • Increase in FA synthesis
• Increase triglycerides
  
  • Increase LPL
  • Inhibits hormone sensitive lipase

Question 17

How does glucose stimulate the release of insulin?

Answer 17

1. Glucose enters the β-cells through the glucose transporters, GLUT2.
2. The glucose that enters the β-cell is phosphorylated to glucose-6-phosphate by glucokinase
3. Glucose-6-phosphate enters glycolytic pathway, leading to a rise in the ATP:ADP ratio within the cell.
4. An increased intracellular ATP:ADP ratio closes the ATP-sensitive potassium channel.
5. Upon depolarization, voltage-gated calcium ion (Ca2+) channels open, allowing calcium ions to move into the cell by facilitated diffusion.
6. The significantly increased amount of calcium ions in the cells’ cytoplasm causes the release into the blood of previously synthesized insulin, which has been stored in intracellular secretory vesicles.

Question 18

Aside from glucose, what other factors stimulate the release of insulin?

Answer 18

• FFAs
• Amino acids
• Sulfonyurea drugs
• Epinephrine and norepinephrine
  *

Question 19

A healthy person will have a spike of insulin within ____ minutes of eating.

Answer 19

60

*There’s a drop and then another slight increase of insulin within 120 minutes of eating. This 2nd peak is caused by reload of beta cells, which are synthesizing more insulin

Question 20

What is the one time in which glucagon and insulin work together?

Answer 20

When amino acids levels are high

Question 21

________ mg/dL of glucose is the “magic mark” where glucagon is shut down and insulin begins to rise.

Answer 21

80

Question 22

When do growth hormone and cortisol come into play with regard to hypoglycemia?

Answer 22

When fasting for 2 or more days

NOTE: The kidneys can also produce glucose by gluconeogenesis in cases of prolonged fasting.

REMEBER: Glucagon and epinephrine are the first hormones to kick in when blood glucose is low. Cortisol and GH supplement them

Question 23

Type I DM

Answer 23

• Diabetes B- cell destruction
  
  • Immmune-mediated
  • Idiopathic​

NOTE: Autoantibodies are formed against islet cell cell autoantibodies, insulin, and GAD65

Question 24

Type II DM

Answer 24

• Progressive insulin secretory defect
  
  • Gestational diabetes mellitus (3rd trimester of preganancy)
  • MODY
  • Disease of the exocrine pancreas (cystic fibrosis)
  • Drug or chemical induced diabetes

Question 25

What are the general signs and symptoms of DM?

Answer 25

• Polyrua, nocturia, polydipsia
• Weight loss, sometimes with polyphagia
• Blurred vision
• Impairment of growth
• Susceptibility to certain infections
• Hyperglygemia with keto acidosis
• Hyperglycemic Hyperosmolar syndrome

NOTE: Ketoacidosis is generally associated with Type I. Type II is associated with hyperosmolar hyperglycemic syndrome (HHS).

Question 26

________ cell loss to a certain degree triggers Type I DM.

Answer 26

Beta

NOTE: Immunologic trigger can lead to diabetes in people with genetic predisposition to it. When an immunologic trigger you can see beta cell numbers steadily dropping.

Question 27

What are the metabolic consequences of insulin deficiency?

Answer 27

• Increased blood glucose concentration
• Increased blood FFA and ketoacid concentration- fat depletion
• Increased blood amino acid concentration- protein depletion

Question 28

What are the consquences of DM Type I on fluids and electrolytes?

Answer 28

• Metabolic acidosis
• Glycosuria and osmotic diuresis
• Increased plasma osmolality
• Hyperphagia
• Polydipsia
• Hypovolemia and hypotension
• Coma and death

Question 29

MODY

Answer 29

Refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production.

NOTE: Genes affected are HNF-4a, HNF-1a, IPF-1, HNF-1B, NeuroD1

Question 30

Contrast MODY from DM II

Answer 30

MODY

• Nonobese
• Monogenic
• Metabolic syndrome absent

DM II

• Obese
• Polygenic
• Metabolic syndrome present

Question 31

How does exercise affect GLUT4 transporters?

Answer 31

Exercise activates GLUT4 so that it is translocated to the plasma membrane of skeletal muscle cells, allowing glucose to enter

Question 32

What are the secondary causes of diabetes mellitus?

Answer 32

• Acromegaly
• Cushing’s syndrome
• Glucagonoma
• Pheochromocytoma
• Hyperthyroidism
• Somatostatinoma
• Aldosteronoma

Question 33

_________ is the first line of treatment for Type II DM.

Answer 33

Metformin

NOTE: It is controversial and is thought to reduce gluconeogenesis in the liver

Question 34

Aside from metformin, which drugs are most oftern prescribed to treat DM Type II?

Answer 34

Biguanides

Sulfonylureas

Question 35

Hyperglycemic Hyperosmolar syndrome (HHS) symptoms

Answer 35

• Altered level of consciousness
• Neurologic signs including: blurred vision, headaches, focal seizures, myoclonic jerking, reversible paralysis
• Motor abnormalities including flaccidity, depressed reflexes, tremors or fasiciculations
• Hyperviscosity and increased risk of blood clot formation
• Dehydration
• Weight loss
• Nausea, vomiting, and abdominal pain
• Weakness
• Low blood pressure with standing

Question 36

Diagnostic criteria for HHS

Answer 36

• Plasma glucose level >30 mmol/L (>600 mg/dL)
• Serum osmolality >320 mOsm/kg
• Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia))
• Serum pH >7.30
• Bicarbonate >15 mEq/L
• Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L)
• Some alteration in consciousness
• BUN > 30 md/dL (increased)
• Creatinine > 1.5 mg/dL (increased)