Lecture 3: Insulin

Question 1

Insulin

Answer 1

Primary defense against hyperglycemia

Without it, cells starve even when surrounded by glucose

Question 2

Types of Diabetes

Answer 2

Diabetes Mellitus- Characterized as hyperglycemia as glucose is unable to enter the cell
Diabetes Insipidus- Disorder of water pressure do to vasopressin resistance or the inability to respond to vasopressin
Diabetes- Passing through urine
Mellitus- Sweet
Insipidus- Bland

Question 3

History of Insulin

Answer 3

1550BC- Egyptian papyrus first describes polyuric states
5-6 BC- Sweet taste of urine, origin of name
1776- Serum also found to be sweet, suggested a systematic disorder
1869- Discovery of the isles of Langerhans by a German medical student
1889- Pancreatomy of a dog found to cause diabetes
1921- Discovery of Insulin
1958- Fred Sanger determined the sequence of bovine insulin, previously thought that proteins were amorphous blobs
1969- 3D structure of insulin discovered
1977- Measured amount of insulin with radioactive immune assay
1976- Recombinant insulin was the first DNA biotechnology drug made by synthesizing the A and B chain separately, succeeding by making insulin in E. Coli

Question 4

Discovery Team

Answer 4

Frederick Banting- Primary motivating force
Charles Best- Medical student, won position in coin toss
James Collip- Biochemist who first isolated insulin
JJR Macleod- Department head, away on vacation
Frederick Banting and JJR Macleod won the Nobel Prize
Banting shared prize money with Best and Macleod shared prize money with Collip

Question 5

Insulin- Discovery to Treatment Time

Answer 5

One year

Typical timeline spans 15 years

Question 6

Nicholae Palescu

Answer 6

Discovered agent that could lower blood glucose in dogs- called it pancreine
Supporter of the anti-semitic movement and was a creationist- part of the reason that his accomplishments are not recognized today- is this right?

Question 7

Pancreas

Answer 7

Highly vascularized
Made up of exocrine and endocrine cells
Exocrine Cell- Secretes digestive enzymes that move through the ducts
Endocrine Cells- Secrete hormones that into the blood stream through the isles of Langerhans

Question 8

Pancreatic Islet

Answer 8

Insulin B cell- Secrete insulin during hyperglycemia
Glucagon A cell- secretes glucagon during times of hypoglycemia
Pancreatic Polypeptide Cells- Secrete PP- used for satiety, secreted during/after meal
Ghrelin- Epsilon- Increases appetite
Somatostatin Delta- Inhibits glucagon/insulin secretion

Question 9

Insulin Gene

Answer 9

Only expressed in Beta cells

Tightly controlled to replenish stored insulin in beta cell granules

Question 10

Insulin Synthesis

Answer 10

Insulin is folded into the ER ad then cleaved before exocytosis
C peptide binds to a G-protein coupled receptor and has effects on tissues
Insulin stored in granules days/hours before released
C-peptide used to distinguish between Type I and Type II diabetes
Insulin has an A chain and a B chain
Mamallian insulin is highly conserved

Question 11

Insulin Storage

Answer 11

Circulating insulin is a monomer

At nanomolar concentrations- insulin forms a stable hexamer build around a Zn ion

Question 12

Assay

Answer 12

Radio Immune Assay- Allow for us to measure the hormone at nano-molar concentration
Modern- Enzyme-Linked Immunosorbent Assay