Insulin Secretion and Intermediary Metabolism 4

Question 1

What is the function of Insulin?

Answer 1

to lower blood glucose levels

Question 2

Which hormones raise blood glucose levels?

Answer 2

• glucagon
• catecholamines
• somatotrophin
• Cortisol

Question 3

What is Type 1 Diabetes Mellitus

Answer 3

Elevated blood glucose levels where insulin is required to prevent ketoacidosis

Question 4

What is Type 2 Diabetes Mellitus

Answer 4

Elevated blood glucose where insulin is required to prevent ketoacidosis but also related to hypertension and dyslipidaemia. Far more prevalent that T1DM

Question 5

What are complications of Diabetes?

Answer 5

• diabetic retinopathy
• nethropathy
• stroke
• heart attacks

Question 6

Dangerous Glucose Levels?

Answer 6

Below 4.0-5.5mM (hypoglycaemia), brain function is increasingly impaired. Below 2.0mM, there is unconsciousness, coma and death

Question 7

Describe the Pancreatic Islets of Langerhans

Answer 7

• account for 2% of pancreas
• Gap junctions are between cells, along with tight junctions, to allow for a paracrine affect
• Alpha cells produce glucagon
• beta cells produce insulin
• delta cells produce somatotstain (decreases both glucagon and insulin production)

Question 8

Insulin Effects

Answer 8

Increased glyconeogenesis
Increased Glycolysis
Increased amino acid transport and protein synthesis
Decreased Lipolysis
Increased Liponeogenesis

Question 9

Factors Affecting insulin secretion

Answer 9

Increased:

• certain gastrointestinal hormones
• certain amino acids
• Parasympathetic activity
• INCREASED BLOOD GLUCOSE

Decreased:

• Somatostatin
• Sympathetic activity

Question 10

Glucagon Effects

Answer 10

• Increased hepatic glycogenolysis
• Increased Lipolysis
• Increased amino acid transport into the liver
• Increased gluconeogenesis

Question 11

How is blood glucose detected?

Answer 11

• glucose enters beta pancreatic cells via GLUT 2
• glucokinase converts this to glucose-6-phosphate before other metabolic pathways. Glucokinase is the rate limiting step and rate of G6P synthesis governs insulin release

Question 12

Describe Insulin Structure

Answer 12

Synthesised as pre-proinsulin consisting of 3 chains

The C peptide is removed after secretion

Question 13

Describe Insulin Secretion

Answer 13

1) glucose enters through GLUT 2
2) the ATP produced blocks the ATP dependent K Channels
3) This leads to the opening of voltage dependent calcium channels
4) Calcium influx causes exocytosis of insulin containing vesicles

Question 14

What is the Incretin Effect?

Answer 14

Food stimulates more insulin production if given orally as opposed to intravenously

Question 15

Describe GLP-1 and its functions

Answer 15

GLucagon-like Protein 1 is a gut hormone secreted in response to nutrients. It is the transcription product of the proglucagon gene (mainly from L cells). It stimulates insulin production and inhibits glucagon.

It increases satiety and has a short half life due to DPPG-4 breakdown. DPPG-4 can be givent to treat T2DM

Question 16

Describe Insulin receptor structure and function

Answer 16

It is needed as insulin is a polypeptide protein and therefore cannot cross the plasma membrane. The alpha subunit recognizes the 3d structure of insulin and causes a conformational change in the beta subunits which cross into the cytoplasm. Phosphorylation of th tyrosine kinase domains is important in recruiting cytoplasmic substrates. This ultimately effects the cell metabolism

Insulin resistance lies in the post-receptor cytoplasmic events and not the receptor itself