19. Acute exercise, Insulin Resistance and diabetes

Question 1

why is insulin produced?

Answer 1

• regulation of glucose homeostasis
• Insulin acts on hepatocytes, myocytes and adipocytes to alter plasma glucose levels
• following a meal, rising plasma glucose acts as a signal to the pancreas to release insulin. Glucose can then be stored as glycogen in the liver.

Insulin controls many essential cellular functions

Question 2

What is diabetes and how is it associated with a substantial increase in mortality?

Answer 2

Disorder of carb metabolism characterized by high blood sugar levels (hyperglycaemia) and presence of sugar in the urine (glycosuria)

Hyperglycaemia causes glycation of tissues. Chronically this eventually leads to organ damage.
There is an increased prevalence with age.

Question 3

What is type 1 diabetes?

Answer 3

Insulin dependent
onset occurs most often during childhood or young adulthood
Pancreatic beta cells are destroyed
Requires daily injection of insulin
Includes 10-15% of all individuals with diabetes

Question 4

What is type 2 diabetes? had how is this affected by obesity?

Answer 4

non-insulin dependent
Onset occurs gradually during adulthood

• delayed or impaired insulin secretion. Impaired insulin action (insulin resistance). Excessive glucose output from liver

Obesity

• Beta cells are less responsive to increases glucose
• Increased insulin resistance in target cells (adipocytokines)
• Increased fat availability leads to decreased glucose oxidation (glucose-fatty acid cycle)

Question 5

What is the main health risk associated with diabetes

Answer 5

You are twice as likely to die than a normal person - this is the same as if you had CHD
- If you suffer from diabetes and CHD then you are 4.7 times more at risk

Question 6

What methods can be used to measure insulin sensitivity?

Answer 6

1. Hyperinsulinaemic Euglycaemic Clamp - gold standard method
2. Oral Glucose Tolerance test
3. Homeostatic Model Assessment

Question 7

Explain how a Hyperinsulinaemic Euglycaemic Clamp test is performed

Answer 7

1. Flood blood with very high levels of insulin. If you were very sensitive to insulin then there would be a massive GLUT4 activation and a lot of glucose uptake.. If you were resistant, only some uptake but not enough.
   - You then put a cannula into the vein to infuse glucose beck into the vein. There is be a lower infusion rate in an insulin resistant muscle.

You have 2 intravenous lines: 1 anteriograde antecubital line + 1 retrograde dorsal line. The dorsal line hand heated to 40-50 oC to arterialise blood. Infusion of extremely highly concentrated insulin solution.
You infuse insulin to high-physiological levels. Plasma glucose then falls as glucose is taken up. Glucose in then infused back in to maintain Euglycaemia

Hyperinsulinaemia shows zero hepatic glucose production. Rate of glucose infusion = rate of glucose disposal.

Question 8

Explain how insulin sensitivity is measured though the Oral Glucose Tolerance Test

Answer 8

1 intravenous line: 1 anteriograde antecubital line.
- Drink a drink with high glucose levels and then glucose kinetics are monitored for 2 hours post-drink to decide on insulin sensitivity..
You must come into the lab fasted.

Question 9

Explain how insulin sensitivity can be measured through the Homeostatic Model Assessment

Answer 9

3 fasting venous blood samples are measured for glucose and insulin.
Sensitivity is expressed as a function of fasting plasma glucose and insulin concentration giving an index of relative insulin resistance.

Question 10

Effects of single exercise bouts for improving glucose uptake?

Answer 10

• Plasma membrane transporters increase after exercise to peak at 1.5 hours after (golden window of opportunity to get the carbs in)
• Exercises causes rises in calcium which may help GLUT 4 translocation.
• More AMPK activation due to calcium.
• AICAR increases AMPK activity and increase GLUT4 translocation
• A muscle contraction enhances the insulin activation of intermediates for the translocation of GLUT4 transporters through an increase in AMPK.
• Production of more GLUT4
• Lowering f PI3-kinase

Question 11

Outline the mechanisms that can improve the uptake of glucose in skeletal muscle…

Answer 11

• Increasing perfusion of active muscle increases exposure to target tissue
• Translocation of GLUT4 to cell membrane - regulated by intracellular calcium… AMPK… nitric oxide
• Sensitisation of insulin response
• Increased expression of GLUT4 gene
• Increased glycogen synthase activity