regulation of blood glucose by pancreatic hormones

Question 1

what are the 2 distinctly different states in which the body must provide energy for cellular activities?

Answer 1

absorptive state and post absorptive state

Question 2

what happens in the absorptive state?

Answer 2

Ingested nutrients enter bloodstream from GI tract
These nutrients support energy requirements of the body
Excess nutrients are stored (for use in post-absorptive state)

Question 3

what happens in the post-absorptive state?

Answer 3

No nutrients are entering bloodstream from GI tract
Switch to net catabolism of stores- breakdown of glycogen, fat and protein
The post-absorptive state must maintain blood glucose levels in the absence of absorption from the GI tract (brain normally only uses glucose for energy)

Question 4

how does the liver produce glucose?

Answer 4

via glucogenesis and glycogen breakdown

Question 5

where is glucose stored?

Answer 5

in adipose tissue as triglycerides, in the liver as glycogen or in muscle as glycogen

Question 6

what hormone is responsible for regulation of blood glucose?

Answer 6

insulin

Question 7

where is insulin secreted?

Answer 7

pancreatic islets ( islets of langerhans) contain cells that secrete insulin and glucagon

Question 8

what are the cells that secrete insulin?

Answer 8

beta cells

Question 9

what are the cells which produce glucagon?

Answer 9

alpha cells

Question 10

which state is insulin released?

Answer 10

absorptive state

Question 11

what does insulin do in the liver?

Answer 11

increases glucose uptake
increases glycolysis
increases glycogen synthesis
inhibits glucogenesis
inhibits glycogen breakdown

Question 12

what does insulin do in the skeletal muscle?

Answer 12

 Increased glucose uptake
 Increased glycolysis
 Increased glycogen synthesis
 Inhibition of glycogen breakdown

Question 13

what does insulin do in the adipose tissue?

Answer 13

 Increased glucose uptake
 Increased glycolysis
 Increased triglyceride synthesis

Question 14

what regulates the release of insulin form beta cells?

Answer 14

glucose

Question 15

how does glucose regulate insulin release from pancreatic beta cells

Answer 15

A. Increased uptake and metabolism of glucose leads to an increase in ATP:ADP ratio
B. Increased ATP:ADP leads to closure of ATP-sensitive K+ channels and membrane depolarisation
C. Depolarisation of membrane leads to opening of voltage-gated Ca2+ channels
D. Resulting increase in cytosolic [Ca2+] promotes secretion of insulin via exocytosis of insulin granules

Question 16

what happens when insulin binds to its receptor?

Answer 16

1. Binding of insulin to the insulin receptor (IR) leads to receptor auto-phosphorylation
2. Phosphorylated residues on the IR act as binding sites for insulin receptor substrate (IRS) proteins
3. IR phosphorylates IRS proteins
4. Phosphoinositide 3-kinase, binds to phosphorylated residues on IRS proteins, and then converts the membrane lipid PIP2 into PIP3
5. Binding to PIP3 activates PDK1, which then phosphorylates and activates protein kinase B (PKB; aka Akt)
6. Activated PKB mediates many of the intracellular effects of insulin.

Question 17

how does insulin stimulate glucose uptake into skeletal muscle and adipocytes?

Answer 17

It does this by increasing the amount of a specialised glucose transporter called GLUT4 at the cell surface

Protein kinase B activation is a key step that regulates insulin-stimulated GLUT4 vesicle exocytosis

Question 18

what is the activity of glycogen synthase regulated by?

Answer 18

phosphorylation:

Insulin signalling leads to activation of PKB

PKB phosphorylates and inactivates GSK

This leads to an increase in the active form of glycogen synthase (non-phosphorylated)

Increased activity of glycogen synthase increases glycogen synthesis

Question 19

what is the transcription factor that regulates glucogenesis?

Answer 19

the transcription factor Fox01

Question 20

where is Fox01 synthesised?

Answer 20

in the cytosol and moves to the nucleus to preform its function.

Question 21

how does insulin inhibit glucogenesis in the liver?

Answer 21

by affecting transcription of glucogenic genes. It activates PKB which phosphorylates Fox01, preventing it from entering the nucleus. This turns off expression of gluconeogenic genes.

Question 22

how does type 1 diabetes arise?

Answer 22

Type 1 diabetes arises due to a loss of insulin synthesis/release from pancreatic beta cells (autoimmune destruction of beta cells)

Question 23

how does type 2 diabetes arise?

Answer 23

Type 2 diabetes is associated with insulin resistance of target tissues and decreased insulin secretion (contribution of these factors differs between individuals)

Question 24

how is type 1 diabetes treated?

Answer 24

insulin

Question 25

how is type 2 diabetes treated?

Answer 25

Type 2 (typical treatment options):
-Diet and lifestyle,
-metformin (suppresses gluconeogenesis),
-sulfonylureas (increase insulin release from pancreatic beta cells),
-insulin

Question 26

what does glucagon do in the post absorptive state?

Answer 26

prevents hypoglycemia.
NB- although glucagon
Type 2 (typical treatment options): Diet and lifestyle, metformin (suppresses gluconeogenesis), sulfonylureas (increase insulin release from pancreatic beta cells), insulin plays a significant role in metabolic changes that take place in the post absorptive state, the reduction in insulin levels is most important for these changes

Question 27

what happens when glucagon binds to its receptor?

Answer 27

leads to an elevation in cAMP levels and activation of protein kinase A (PKA)

Question 28

what does PKA do?

Answer 28

1. PKA phosphorylates PK (phosphorylase kinase), increasing its activity
2. PKA phosphorylates glycogen synthase, decreasing its activity

Question 29

what does leptin do?

Answer 29

When fat storage hits a certain level LEPTIN is released from adipocytes. Activation of leptin receptors in the hypothalamus leads to changes in the sensation of hunger
(“satiety hormone”)

Question 30

what does ghrelin do?

Answer 30

Cells in the GI tract release GHRELIN when the stomach is empty. Acts on receptors in the hypothalamus to increase hunger
(“hunger hormone”)

Question 31

what does glucose-like peptide-1(GPL-1) do?

Answer 31

Cells in the GI tract secrete Glucagon-like peptide-1 (GLP-1) in response to the presence of nutrients. It increases glucose-stimulated insulin release and suppresses glucagon secretion