Lecture 2 - major factors regulating insulin secretion and effects

Question 1

What substances secreted by the GI mucosa stimulate insulin secretion?

Answer 1

Glucagon, glucagon derivatives, secretin, cholecystokinin and gastric inhibitory peptide.

Question 2

What is the incretin effect ?

Answer 2

incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism

Question 3

What does the incretin effect tell us about those who have diabetes?

Answer 3

It tells us that they are not responding correctly to oral glucose because there is a diminished incretin effect.

Question 4

Where is glucagon-like polypeptide 1 (GLP-1) synthesized?

Answer 4

by L cells in the ileum, colon and less often in the duodenum and jejunum.

Question 5

What does GLP-1 do?

Answer 5

1. ) Stimulates insulin secretion
2. ) Supresses glucagon secretion
3. ) slows gastric emptying
4. ) reduces food intake
5. ) increases Beta cell mass
6. ) maintains Beta cell function
7. ) improves insulin sensitivity

These effects are reduced in people with type 2 diabetes

Question 6

What does exendin-4 do and what has it been used for?

Answer 6

Stimulates insulin release which lowers blood sugar. It has results in the development of byetta which is a synthetic exendin-4 which is used as a treatment for diabetes.

Question 7

Effect of insulin on the liver?

Answer 7

Increases glycogen synthesis and glycolysis by using blood sugar. It decreases gluconeogensis to stop you making sugar from fat.

Question 8

Effect of insulin on the Fat?

Answer 8

Increase glucose transport and lipgenesis. Decreases liplysis.

Question 9

Effect of insulin on the Skeletal muscle ?

Answer 9

Increases glucose transport and glycogen synthesis. Decreases gluconeogenesis.

Question 10

What does insulin stimulate?

Answer 10

It stimulates Phosphofructokinase-1 and pyruvate kinase.

Question 11

What inhibits lipases and why?

Answer 11

Insulin inhibits lipases to stop breaking down fat to use as energy.

Question 12

What is the structure and half life of glucagon?

Answer 12

It is a peptide hormone that has 29 AA and is produced by alpha cells. Its half life is 5-10 mins and it is degraded particularly by the liver tissue.

Question 13

What are the factors that increase the secretion of glucagon?

Answer 13

1. ) When blood glucose is less than 70.
2. ) AAs are high like in a high protein low carb meal
3. ) Stress: adrenaline via Beta adrenergic receptors on alpha cells.

Question 14

What are some factors that decrease the secretion of glucagon?

Answer 14

1. ) increase blood glucose

2. ) insulin

Question 15

What organs and tissues are the main targets for glucagon?

Answer 15

1. ) liver
2. ) muscle
3. ) adipose tissue

Question 16

glucagon …… cyclic AMP and ….. PKA activity?

Answer 16

increases , increases

Question 17

Glucagon …… IP3 pathway ….. Ca2+

Answer 17

activates, increasing

Question 18

What are the actions of glucagon in the liver?

Answer 18

1. ) increase in glycogenolysis by activating phosphorylase which cleaves a glucose-1-P off glycogen
2. ) Inhibits glycogenesiss by inactivating glycogen synthase by phosphorylation
3. ) increased gluconeogenesis by increasing phosphoenolpyruvate carboxykinase

Question 19

What are the actions of glucagon in lipids?

Answer 19

1.) increases liplysis by activating lipases which break down TAGs. It also inhibits the acetyl CoA carboxylase which stops FFA from acetyl CoA.

Question 20

What is the response of the body to dropping glucose levels?

Answer 20

1. ) decreased insulin - glycemic threshold - 80-85mg%: primary first defence
2. ) Increase in Glucagon - 65-70 mg%: primary second defense
3. ) Increase in epinephrine - 65-70 mg%: Critical third defense
4. ) Increase in cortisol and GH - 65-70 mg%
5. ) increase in food ingestion - 50-55 mg%

Question 21

What does somatostatin do?

Answer 21

It inhibits the secretion of: GH, insulin, Glucagon, exocrine pancreatic secretions.

Question 22

What are the forms of somatostatin?

Answer 22

SS-14 : sole isoform from pancreas, major isoform in CNS
SS-28 : Major isoform in the intestine

14 and 28 are the amino acid lengths. Also, 28 is 10x more potent in the inhibition of GH secretion whereas 14 is more potent at inhibiting glucagon release.

Question 23

What are the complication involved with diabetes?

Answer 23

1. ) Diabetic retinopathy: cause of blindness
2. ) Stroke: 2-4 incerase in death from it
3. ) CVS disease: 8/10 of diabetes people die from it
4. ) Diabetic peripheral neuropathy: initiating factor of diabetic foot ulceration
5. ) Diabetic neuropathy: end stage renal disease

Question 24

Symptoms of diabetes mellitus?

Answer 24

1. ) Polyphagia - no glucose enters the cell which causes hunger
2. ) Hyperglycaemia - blood glucose is increased
3. ) Glucosuria
4. ) Polyuria - glucose drags water into the urine
5. ) Polydipsia - Increased thirst to replace water loss

Question 25

What is MODY or maturity onset diabetes of the young?

Answer 25

A group of monogenic disorders that are characterised by autosomal dominantly inherited non insulin dependent form of diabetes, typically in young adults before the age of 25.

Question 26

What is type 2 DM?

Answer 26

It is non insulin dependant and usually happens in adults. It is because of insulin resistance which can lead to beta cell exhaustion. This resistance begins about 10 years before diagnosis. More common in people over 40 but may happen in kids.

Question 27

What is type 1 DM?

Answer 27

Insulin dependant diabetes and a juvenile onset. It accounts for 5-10 percent of patients with diabetes. There is an insulin deficiency which results in the destruction of pancreatic beta cells.