5- Introduction To Diabetes Mellitus Flashcards
What are the effects of insulin
Glucose Decrease hepatic glucose output Increase uptake of glucose by muscles • Protein Decreased proteolysis • Lipid Decreased lipolysis Decreased ketogenesis
• Other effects: Growth Vascular Effects Smooth muscle hypertrophy Ovarian Function Clotting Energy Expenditure
Describe the uptake of glucose through GLUT4
Glucose is mainly taken up by Glucose Transporter 4 (GLUT-4)
• GLUT-4 is particularly abundant in muscle and adipose tissue
• Insulin stimulates glucose transporter 4
• It has hydrophobic elements on the outside embedded in the membrane and a hydrophilic core which allows glucose into the cell - it is insulin sensitive
• GLUT-4 sits in vesicles within the cytoplasm - insulin recruits them to the membrane thus causing up to 7-fold increase in glucose uptake
Describe the effect of glucose on proteins
Insulin stops proteolysis
• Cortisol increases proteolysis when we’re stressed
• Amino acids could be oxidised in the muscle cell and insulin
prevents oxidation of amino acids
• Insulin increases the re-synthesis of proteins from amino acids
Somatotrophin and Cortisol have contradicting effects - so it isn’t a case of the four counter-regulatory hormones (Somatotrophin, Cortisol, Catecholamines and Glucagon) against Insulin
• The amino acids could get in to the circulation and move to the liver where it can be used to produce glucose
What are the effects of glucose In The liver
Gluconeogenic amino acids enter the liver via specific transporter channels
• Glucagon increases the uptake of amino acids by the liver
• In the liver, protein synthesis is stimulated by insulin
• The amino acids can, however, be used to make glucose - GLUCONEOGENESIS
• Insulin inhibits gluconeogenesis
• Somatotrophin, Cortisol, Catecholamines and Glucagon increase gluconeogenesis
• The glucose produced from gluconeogenesis can then enter the circulation as HEPATIC GLUCOSE OUTPUT (HGO)
What are the effects of insulin on adipocytes
Triglycerides come in the vasculature and are too big to enter the adipocyte directly
• Triglycerides have to be broken down by LIPOPROTEIN LIPASE before it can enter the adipocyte
• Lipoprotein Lipase is stimulated by insulin
Triglyceride is broken down into glycerol and non-esterified fatty acids which are absorbed into the adipocyte
• Glucose also enters the adipocyte and can be used to make NEFA
• Glucose can also be chopped up to make two glycerols and the fatty acids can
be stuck to the glycerol to make triglycerides
• Insulin will stop lipolysis and the four counter-regulatory hormones will
promote lipolysis
• So insulin has TWO effects on fat depending on where it acts:
Blood - breaks down the fats so that it can enter the adipocyte Adipocyte - promotes formation of triglyceride and storage of fat and inhibits lipolysis
How is glycerol used by the liver
Glycerol coming from adipocytes and food enters the liver
• This glycerol is used to make Triglycerides
• The triglycerides can then enter lipoprotein particles
• Glycerol could also be used to make glucose - form of gluconeogenesis
• Two glycerols can, in effect, be stuck together to make glucose - this supports HEPATIC GLUCOSE OUTPUT
• Glycerol can be used to make glucose but fat CANNOT re-enter the glucose pathway
• After a fast of 10 hours, 25% of our hepatic glucose output is supported by new glucose production
What substances can the brain use as fuel
Glucose
Ketone bodies
How does insulin effect ketone body synthesis in the liver
• Fatty acids generated from lipolysis can enter the liver and be used to make ketone bodies
• Insulin INHIBITS the conversion of Fatty Acyl CoA to Ketone Bodies
• Glucagon PROMOTES the conversion of Fatty Acyl CoA to Ketone Bodies
• Ketone bodies will enter the circulation and mainly be used by the muscles
• KEY POINT: If someone has high
insulin then they should stop making ketone bodies
• High Blood Glucose + High Ketone Bodies = INSULIN DEFICIENT
Although ketones are normal while fasting but not with high sugar levels in Blood.
How does insulin effect glygogenlysis
Glucose enters the liver and is converted to Glucose-6-Phosphate
• Insulin promotes the STORAGE of glucose as glycogen
• Glucagon and Catecholamines promotes GLYCOGENOLYSIS
How does insulin effect uptakeof glucose by muscle
Glucose enters muscle through GLUT-4
• Insulin PROMOTES uptake of glucose by
GLUT-4
• Stress hormones tend to INHIBIT uptake
of glucose by GLUT-4
• Glucose can then be stored as glycogen in
the muscle but is mainly used as a fuel source
What is a normal glucose concentration
3-5.5 mol/l
What happens when fasting
Low Insulin:Glycogen ratio
• Blood glucose concentration is NORMAL because the change in Insulin:
Glucagon ratio maintains a normal blood glucose concentration
• Muscle use lipid
• Brain uses glucose and then, at a later stage, ketone bodies
• INCREASE IN:
Concentration of NEFA
Proteolysis
Lipolysis
Hepatic Glucose Output (from glycogenolysis and gluconeogensis)
• DECREASE IN:
Amino Acid Concentration (when prolonged)
What happens after eating
High Insulin:Glucagon ratio • Stored insulin is released then you get 2nd phase insulin release • Stop Hepatic Glucose Output • INCREASE IN: Glycogen Protein Synthesis Lipogenesis • DECREASE IN: Gluconeogenesis Proteolysis
What are the effects of insulin deficiency
Proteolysis with weight loss
• Hyperglycaemia
• Glycosuria with osmotic symptoms (polyuria and polydipsia)
• Ketonuria
What happens during hyperglycaemia induced by insulin
Glucose enters muscle
• INCREASE IN:
Insulin - because you’ve given insulin to cause this hypoglycaemia Glucagon
Catecholamines
Cortisol
Somatotrophin
• DECREASE IN:
HGO
Lipolysis
• Subcutaneous Insulin is involved in switching off HGO
• Intramuscular Glucagon can trigger an increase in HGO
