the endocrine pancreas

Question 1

Different islet endocrine cell types (5)

Answer 1

• α-cells secrete glucagon
• β-cells secrete insulin
• δ-cells secrete somatostatin
• PP-cells secrete pancreatic polypeptide(PP)
• ε-cells secrete Ghrelin

Question 2

Role of the K+ ATP channel & electrical activity in beta cell glucose sensing- low glucose

Answer 2

the KATP channel is open, maintaining a hyperpolarised plasma
membrane

Question 3

Role of the K+ ATP channel & electrical activity in beta cell glucose sensing- high glucose

Answer 3

closure of the KATP channel depolarises the PM, triggering
insulin secretion.

Question 4

Role of the K+ ATP channel & electrical activity in beta cell glucose sensing

Answer 4

Sulfonylureas bind the SUR1 subunit of the KATP channel, closing the channel and triggering insulin secretion irrespective of glucose concentrations

Question 5

SUR1

Answer 5

sulphonylurea receptor subtype 1

Question 6

Kir6.2

Answer 6

inwardly rectifying K+- channel, subtype 6.2

Question 7

Sulfonylurea (SU) treatment of T2DM (4)

Answer 7

MOA: pharmacological inhibition of KATP channels depolarises beta cell mamebranes independently of glucose metabolism

• Use in T2D: Glucose control good in short term, poor in long term, good treatment for some forms of monogenic diabetes
• First gen: e.g. Tolbutamide.
• Second gen: e.g. glibenclamide, gliclazide

Question 8

Insulin granule exocytosis(3)

Answer 8

insulin release

-10,000 secretory granules per β-cell –<1,000 released/day

-8 fg insulin per secretory granule

Question 9

Beta cells sense more than glucose (17)

Answer 9

Beta cells respond to nutrients,
hormones and neurotransmitters and
secrete appropriate amounts of insulin

-Free fatty acids
-Glucose
-Amino acids
-Muscle
-Fat
-Liver
-Gut
-Alpha cells
-IL6
-Leptin
-Adiponectin
-Igf1
-Glucagon
-GLP1
-GIP
-Acetycholine

Question 10

Beta cell failure occurs in

Answer 10

both type 1 and type 2 diabetes

Question 11

beta cell fail- type 1

Answer 11

Type 1 diabetes and LADA
(Latent Autoimmune Diabetes in Adults):
autoimmune destruction of beta cells = insulin deficiency

Question 12

beta cell fail- type 2

Answer 12

Insulin resistance + beta cell dysfunction = relative insulin deficiency

Question 13

Metabolic disease and the beta cell (4)

Answer 13

-Glucose tolerant
-Obese/Insulin resistant β-cell compensation
-β-cell failure
-Overt T2DM

Question 14

beta cell summary (6)

Answer 14

Pancreatic islets are composed of 3 principle endocrine cells types (alpha, beta, delta), of which beta cells are the most numerous

Beta cells secrete insulin in a biphasic manner in response to glucose stimulation (and switch off rapidly at low glucose)

Insulin drives anabolic pathways in target tissue to promote storage of nutrients and lower blood glucose

Beta cells respond to numerous nutrients and hormones besides glucose to coordinate insulin secretion

Relationship between insulin secretion and insulin sensitivity is highly variable between individuals.

Impaired insulin secretion is a hall mark of type 2 diabetes, but can recovered in some individuals following caloric restriction

Question 15

Islet defects in T2DM (4)

Answer 15

Impaired insulin secretion.

Dyregulated glucagon secretion=
-Lack of suppression of GCG secretion at high glucose
-May contribute to hyperglycaemia

Question 16

Alpha cell summary (3)

Answer 16

Alpha cells secrete glucagon inversely proportional to blood glucose, in contrast to pancreatic beta cells.

Glucagon acts on the liver to promote hepatic glucose production, raising blood glucose.

Glucagon secretion is elevated in the fed state in T2D and contributes to hyperglycaemia

Question 17

Characteristics of Insulin, Glucagon (and other hormones) (6)

Answer 17

Production as an inactive prohormone precursor.

Processed via classical secretory pathway (viaGolgi)*.

Stimulus-secretion coupling.

Soluble factor.

Dose dependent effect at target tissue.

Sufficiently-short serum half life.

Question 18

Secretin (2)

Answer 18

Secreted by duodenal S-cells in response to increased acidity

Controls gut pH by stimulating bicarbonate release from the exocrine pancreas, and inhibiting gastric acid release from parietal cells of stomach

Question 19

Exocrine

Answer 19

Amylase secretion from
acinar cells.

Question 20

Endocrine

Answer 20

Insulin secretion from beta
cells (action on muscle)

Question 21

Paracrine

Answer 21

Somatostatin secretion from delta
cells (action on alpha cells)

Question 22

Autocrine

Answer 22

Insulin secretion, action on beta cells.

Question 23

Juxtacrine

Answer 23

Notch signalling during development