Title: Endocrine / Physiology / Insulin

Q: Preproinsulin synthesized in ?
A: RER of pancreatic β cells

Q: Proinsulin stored in ?
A: secretory granules

Preproinsulin > cleavage of “presignal” > proinsulin > cleavage of proinsulin > exocytosis of insulin and C-peptide equally.

Both insulin and C-peptide are high  in endogenous insulin secretion.

Q: Examples of endogenous insulin secretion:
A: - type 2 DM
- insulin secretagogues
- insulinoma

Q: [...] insulin lacks [...].
A: Exogenous; C-peptide

Q: Insulin is synthesized in ?
A: pancreas

Q: Insulin is cleared by both [...] and [...].
A: liver; kidneys

Q: Insulin binds insulin receptors (tyrosine kinase
activity), inducing glucose uptake (carrier mediated transport) into....?
A: insulin-dependent tissue and gene transcription.

Binds insulin receptors (tyrosine kinase activity) [1], inducing glucose uptake (carrier-mediated transport) into insulin-dependent tissue [2] and gene transcription

Anabolic effects of insulin:
- ↑ glucose transport in skeletal muscle and adipose tissue.
- ↑ glycogen synthesis and storage
- ↑ triglyceride synthesis
- ↑ Na+ retention (kidneys)
- ↑ protein synthesis (muscles)
- ↑ cellular uptake of K+ and amino acids
- ↓ glucagon release
- ↓ lipolysis in adipose tissue

Q: Unlike [...], insulin does not cross placenta.
A: glucose

Q: In mothers with diabetes, excess glucose can
[...] placenta and ↑↑ [...].
A: cross; fetal insulin

Q: Insulin-dependent glucose transporters:
A: GLUT 4

Q: Insulin-independent transporters:
A: - GLUT 1
- GLUT 2
- GLUT 3
- GLUT 5

Q: GLUT4 found in...?
A: - Adipose tissue
- Striated muscle

Q: What can also ↑ GLUT4 expression ?
A: exercise

Q: GLUT1 found in...?
A: - RBCs
- Brain
- Cornea
- Placenta

Q: GLUT2 (bidirectional) found in...?
A: - β islet cells
- Liver
- Kidney
- GI tract (think 2-way street)

Q: GLUT3 found in...?
A: - Brain
- Placenta

Q: GLUT5 (Fructose) found in...?
A: - Spermatocytes
- GI tract

Q: SGLT1/SGLT2 (Na+-glucose cotransporters) found in...?
A: - Kidney
- Small intestine

Brain prefers glucose, but may use ketone bodies during starvation.

RBCs utilize only glucose, as they lack mitochondria for aerobic metabolism.

Q: BRICK LIPS (insulin-independent glucose
uptake):
A: - Brain
- RBCs
- Intestine
- Cornea
- Kidney
- Liver
- Islet (β) cells
- Placenta
- Spermatocytes

Q: What is the major regulator of insulin release ?
A: Glucose

Q: ↑ insulin response with oral vs IV glucose due to....?
A: incretins (eg, [GLP-1] & [GIP]) which are released after meals and ↑ β cell sensitivity to glucose. Release ↓ by α2, ↑ by β2 stimulation (2 = regulates insulin).

Q: What are the main incretins ?
A: - Glucagonlike peptide 1 [GLP-1]
- Glucose-dependent insulinotropic polypeptide[GIP]

↑ insulin response with oral vs IV glucose due to incretins (eg, [GLP-1], [GIP]), which are released after meals and ↑ β cell sensitivity to glucose. Release ↓ by α2, ↑ by β2 stimulation.          (2 = regulates insulin).

3. Glucose enters β cells
4. ↑ ATP generated from glucose metabolism
5. closes K+ channels (target of sulfonylureas)
6. and depolarizes β cell membrane .
7. Voltage-gated Ca2+ channels open → Ca2+ influx
8. and stimulation of insulin exocytosis.