Insulin Secretion and Intermediary Metabolism

Question 1

Basic feedback loop of blood glucose-affecting hormones?

Answer 1

Increased blood glucose concentration
Increased insulin secretion response
Decreased blood glucose concentration
Increased secretion of glucagon, catecholamines, somatotrophin, cortisol to raise it again

Question 2

Percentage of pancreas involved in exocrine and endocrine function?

Answer 2

Exocrine = 98% (into duct)
Endocrine = 2% (into circulation)

Question 3

Name of pancreatic tissue associated with endocrine secretion?

Answer 3

Islets of Langerhans

Question 4

Which 3 cell types lie in the Islets of Langerhans and what hormones do they produce?

Answer 4

Alpha cells - glucagon
Beta cells - insulin
Delta cells - somatostatin

Question 5

How can cells within the islets of langerhans demonstrate paracrine control?

Answer 5

The cells are very close together with small gaps between them. These gaps have high hormone concentrations and allow communication between the different cells.
Gap junctions allow small molecules to pass directly between cells and tight junctions for small intercellular space

Question 6

Other than somatotrophin release, what does somatostatin inhibit?

Answer 6

Insulin AND glucagon release via paracrine effects

Question 7

Main stimulus of insulin release?

Answer 7

Increased blood glucose

Question 8

Other stimuli of insulin release?

Answer 8

Glucagon release
Certain GI hormones
Certain amino acids
Parasympathetic nervous activity

Question 9

Inhibitory stimuli of insulin release?

Answer 9

Sympathetic activity

Somatostatin

Question 10

What main effects does increased insulin release have?

Answer 10

Increased glycogenesis
Increased glycolysis
Increased glucose transport INTO cells via GLUT4
OVERALL decrease in blood glucose conc

Question 11

Other effects of insulin release? (still aim of reducing blood glucose)

Answer 11

Increased amino acid transport
Increased protein synthesis
Decreased lipolysis
Increased lipogenesis

Question 12

Main stimulus of glucagon release?

Answer 12

Decreased blood glucose

Question 13

Other stimuli of glucagon release?

Answer 13

Certain GI hormones
Certain amino acids
Sympathetic activity

Question 14

Inhibitory stimuli of glucagon release?

Answer 14

Beta cells secreting insulin
Parasympathetic nervous activity
Somatostatin

Question 15

Main effect of increased glucagon secretion?

Answer 15

Hepatic glycogenolysis

Question 16

Other effects of glucagon release?

Answer 16

Increased amino acid transport into liver for gluconeogenesis
Increased lipless for gluconeogenesis
OVERALL increases blood glucose conc

Question 17

Role of glucokinase in insulin release?

Answer 17

Converts glucose to glucose-6-phosphate, consumption of G6P increases ATP concentration in beta cell leading to insulin release

Question 18

Process of insulin synthesis?

Answer 18

Proinsulin cleaved to form C-peptide + alpha/beta chains of insulin
Disulphide bridges form specific 3D structure of insulin

Question 19

Levels of what can be measured to assess pancreatic function?

Answer 19

C-PEPTIDE

Question 20

Process of beta cell stimulation and insulin release?

Answer 20

Glucose enters via GLUT2 transporter
Glucose is converted by hexo/glucokinase to G6P and ATP
ATP blocks ATP-sensitive K+ channels
VG Ca2+ channels open causing influx of Ca2+ into beta cell stimulating release of preformed insulin and synthesis of NEW insulin

Question 21

Does oral glucose load impact or intravenous glucose load impact insulin production more?

Answer 21

Oral glucose load has a greater impact on insulin production

Question 22

What is GLP-1, why is it released and what effects does it have?

Answer 22

Glucagon-like peptide 1
GI hormone released in response to food
Causes insulin release and decrease in glucagon release
Increases SATIETY so less food is consumed, can be used to help weight loss

Question 23

What is a common T2DM treatment involving GLP-1?

Answer 23

Injected GLP-1 and DPPG-4 inhibitor

DPPG-4 usually breaks down GLP-1 so inhibitor extends the half-life and effect of GLP-1

Question 24

What are the two phases of insulin release?

Answer 24

First phase insulin - stored insulin which is released directly after consuming a meal
Second phase insulin - newly synthesised insulin, released over a couple of hours and increases food storage (glycogenesis)

Question 25

What is the structure of the insulin receptor?

Answer 25

2 cytoplasmic alpha subunits - bind to insulin

2 transmembrane beta subunits - TYROSINE KINASE domains

Question 26

What is the process of inducing insulin’s effects on target cell by binding to its receptor?

Answer 26

Inuslin binds to alpha subunits
Conformational change in tyrosine kinase domains
Autophosphorylation of receptors occurs
Conformational change induces phosphorylation of cell protein substrates and activation of pathways leading to known insulin effects (glycogenesis, protein synthesis etc.)

Question 27

Type 2 diabetes mellitus patients have their abnormality in insulin production, the receptor, or the intracellular pathway?

Answer 27

Type 2 patients are INSULIN RESISTANT.

The abnormality lies in the pathways of insulin action, not the receptor.