Week 9 - Glucose Homeostasis Flashcards
What are the major targets of inulin’s effects?
muscle
- promotes glucose uptake
- promotes protein synthesis
adipose tissue
- promotes glucose and fatty acid uptake
- inhibits lipolysis
liver
- promotes glucose utilisation
- suppress glucose production
- promotes triglyceride synthesis
What is the proximal segment of insulin segment?
- activates tyrosine kinase receptor
- and tyrosine phosphorylation
- of IRS proteins
- which assembles PI3K signalling complex
- generates PtdIns(3,4,5)P3
- which recruits PDK1 and AKT
- PDK1 phosphorylates AKT to partially activate
- AKT phosphorylates mTORC2
- phosphorylates and fully activates AKT
What happens to glucose during fasting?
- hepatic glucose output provides tissues with glucose
- lipolysis with free fatty acids and glycerol from adipocytes
- serve as fuel and provide liver with energy
- and NADH for glucose synthesis by gluconeogenesis
- regulated by glucagon
What is insulin resistance?
-defect in insulin-mediated control of glucose metabolism
- exhibit hyper insulinaemia (higher insulin blood levels)
- ability of insulin is impaired
What is diabetes?
- any disorder that has excessive urine excretion
- diabetes mellitus is the most common form
- caused by disrupted insulin function
- disrupted carbohydrate hemeostasis
- results in hyperglycaemia
- causes micro- and macro-vascular complications
- causes the excess urine excretion of glucose
What is T1DM?
Type 1 Diabetes Mellitus
- hyperglycaemia
- due to insulin deficiency
- by loss of pancreatic islet β-cells
- many cases caused by autoimmunity by formation of autoantibodies
- produced due to β-cell auto antigens exposure
- triggered by genetic / environmental / life style factors
What are the stages of T1DM?
- 3 stages
- all have β-cell autoimmunity by autoantibodies presence
- all have β-cell loss
- hyperglycaemia present in last 2 stages
- symptoms present in last stage
- first 2 stages considered asymptomatic
What is T2DM?
Type 2 Diabetes Mellitus
- impaired insulin secretion
- with pre-existing insulin resistance
What is pre diabetes?
any one of:
- IFG (Impaired Fasting Glucose)
- fasting glucose levels are higher but don’t meet diabetes criteria
- IGT (Impaired Glucose Tolerance)
- increased glycated HbA1c (Haemoglobin A1c)
What is HbA1c?
form of haemoglobin chemically linked to glucose
What is OGTT?
Oral Glucose Tolerance Test
- 8 hours of fasting
- blood sample taken
- blood sugar levels measured
- drink solution with 100 grams of sugar
- blood sugar levels measured in 1, 2, and 3 hours
What are the molecular mechanisms of insulin resistance?
Ectopic lipids and PKCs
- abnormal lipid accumulation
- increases DAG (DiAcylGlycerol) levels
- activates PKCs
- phosphorylate serine in IRS proteins
- inhibit insulin signalling
Mitochondrial dysfunction
- mitochondrial density reduces
- impaired mitochondrial functioning
systemic inflammation
- increased inflammatory cytokines
ER stress
- increase in protein synthesis
- imbalance between demand and capacity of ER
