normal endo pancreas 2

Question 2

incretins are hormones that work to ___insulin secretion. Substantially more insulin secreted in response to ___glucose vs ____glucose.

Answer 2

increase oral intravenous feedforward mechanism : anticipating the rise in blood glucose that would occur following carbs ingestion

Question 3

Glucose in the small intestine stimulates incretin release.What are the 2 main incretins?

Answer 3

GIP (glucose-dependent insulinotropic peptide) GLP-1 (glucagon-like peptide-1).

Question 4

glucose levels are ↑, GLP-1 and GIP signal β cells to ↑ insulin release + ___signals α cells to suppress glucagon release. dipeptidyl-peptidase 4 (DPP-4) degrades active incretins after their release

Answer 4

GLP-1

Question 5

Exenatide (Byetta) is a GLP-1 R agonist for patients with poor control on oral agents. only as injections, twice daily. Sitagliptin: mechanism? advantage over exenatide?

Answer 5

↑ GLP-1 levels by blocking DPP-4 so called DPP-4 inhibitors or gliptinsadvantage; can be taken orally

Question 6

THE INCRETIN EFFECT IS ____INTYPE 2 DIABETES

Answer 6

diminishedLevels of GLP-1 are decreased.The insulinotropic response to GIP is diminished but not absent.

Question 7

Dysregulation of Insulin Secretion____- constitutive insulin secretion from a β cell tumourPersistent Hyperinsulinaemia and Hypoglycaemia in Infancy (PHHI):mutations in the genes encoding the ___receptor + the _____ (Kir) –> hyperinsulinaemia.

Answer 7

Insulinoma sulfonylureaK+ inward rectifier channel

Question 8

Insulin receptor α2β2 heterotetramer : extracellular α subunits =site of ___ transmembrane β subunits = intrinsic receptor____ _____

Answer 8

insulin binding (LBD) tyrosine kinases (RTKs)insulin R highly expressed in skeletal muscle, adipose tissue and liver

Question 9

Receptor Signalling - 1Activated receptor TK phosphorylates __residues on IRS-1 and IRS-2IRS-1,2 act as __proteins

Answer 9

1.Tyr 2. adapter 3.

Question 10

Receptor Signalling - 2phospho-tyrosine residues interact with src-homology (SH)2 domains in downstream signalling proteins: PI3K (inserts ___) + –>PKB –>GSK3  Grb2 –> __Ras –>MAPKK –>MAPK–>translocation into nucleus etc

Answer 10

GLUT4SOS

Question 11

pancreatic β cells have no glycogen, all glucose must enter the islets from plasma via ____

Answer 11

GLUT2

Question 12

glucose transport via GLUT2 is___ glucose enters islet and is rapidly __to G-6-P –> always a steep concentration gradient –> glucose enters β cell from the plasma.

Answer 12

bi-directional,phosphorylated

Question 13

Once phosphorylated, G-6-P, metabolisedby glycolysis –> NAD+ to NADH, –> ATP–> blocks the ATP sensitive ______–> depolarisation, opens voltage sensitive Ca2+ channels.

Answer 13

K+ channel, It is the influx of calcium which stimulates release of insulin granules.

Question 14

In Persistent Hyperinsulinemia and Hypoglycemia in Infancy (PHHI), the ATP sensitive K+ channels are constantly __

Answer 14

closed–> constitutively high insulin secretion