Week 8 Lipids and Insulin Secretion in T2D

Question 1

Give an Overview: role of lipids in insulin

resistance and T2D

Answer 1

Affects 500 mill people worldwide
Step 1
•Progression from normal- to impaired glucose tolerance (IGT)
•Insulin resistance in liver, skeletal muscle and adipose tissue
•Dyslipidaemia (increased TAG, FFAs)
•Hyperinsulinaemia – pancreatic islet/beta-cell compensation
•Maintenance of normoglycaemia

Step 2
•Progression from IGT to overt T2D
•Pancreatic beta-cell failure
•Reduced insulin secretion
•Hyperglycaemia
Type 2 diabetes and insulin resistance

Question 2

Explain how liver is a major site of glucose metabolism

Answer 2

HEPATIC GLUCOSE STORAGE:
PPBS increase > Increase insulin > increase hepatic glucose storage > causes lipogenesis and glycogenesis

HEPATIC GLUCOSE PRODUCTION: (HGP)
PPBS increase > increase insulin > decrease in hepatic glucose production >decrease glycogenolysis and gluconeogenesis

Both result in decrease blood glucose

Insulin-regulated glycogenolysis and HGP – impaired in insulin resistance
• Raised blood glucose

page 6: https://keats.kcl.ac.uk/pluginfile.php/6546110/mod_resource/content/1/Lipids%20and%20type%202%20diabetes-2020.pdf

Question 3

Muscle -Major sites of glucose metabolism explain

Answer 3

1)↑ PPBS
↑ muscle glucose storage
↑ lipogenesis, ↑ glycogenesis

2)↑ PPBS
↑ muscle glucose uptake

Both result in ↓ blood glucose

Insulin-regulated glycogenesis and glucose uptake – impaired in insulin resistance
> Raised blood glucose

Question 4

Overview of Lipid-induced insulin resistance

Answer 4

↑ Serum TG and FA
a) Liver
Due to Tissue Insulin resistance:
↓glycogen production. ↑ gluconeogenesis
↑  hepatic glucose production

b) Adipose
Due to Tissue Insulin resistance:
↓Glycogen production
↓glucose uptake
↓Skeletal muscle glucose uptake

Both result in ↑ blood glucose, systemic IR

page 9: https://keats.kcl.ac.uk/pluginfile.php/6546110/mod_resource/content/1/Lipids%20and%20type%202%20diabetes-2020.pdf

Question 5

Mechanisms of lipid build-up in liver and skeletal muscle

Answer 5

Imbalance between supply/synthesis and demand/utilisation

↑Diet (more SFA) - liver and muscle
↑Denovo Lipogenesis (DNL) - liver
↑Adipose Tissue Storage - liver and muscle

↓Mitochondrial FA oxidation (mainly mus, also liver)
↓VLDL secretion (liver)

Both result in:
↑Hepatic, SK mus, lipid accumulation

page 10: https://keats.kcl.ac.uk/pluginfile.php/6546110/mod_resource/content/1/Lipids%20and%20type%202%20diabetes-2020.pdf