Fed, Fasted and Starvation Flashcards
What is the absorptive state?
Food in the GI tract
Nutrients being absorbed into blood and lymph
What is the post absorptive state?
Fasting state
Nutrients not being absorbed
What do absorbed nutrients enter first?
The portal blood
What organ do absorbed nutrients reach first?
Liver
What nutrients are in the portal blood?
Monosaccharides
Amino acids
Lipids
Which tissues are hormone-sensitive with regards to energy metabolism?
Liver
Muscle
Adipose tissue
Where will glucose in the blood end up?
Liver to store as glycogen
Adipose tissue to form triglycerides
Muscle to store as glycogen
Other tissues for krebs cycle
Where will amino acids in the blood end up?
In the liver to be converted to keto acids and release energy
In muscle to create proteins
Where will triglycerides in the blood end up?
In adipose tissue
What triggers a switch from post absorptive to absorptive state?
Increased glucose and insulin in the blood
What triggers release of insulin and from where?
Secreted by beta cells of the islets of Langerhans in the pancreas
Trigger is high blood glucose and amino acids
What takes up glucose into beta cells?
GLUT-2 transporter
What does uptake of glucsose into beta cells trigger?
Generation of ATP from glucose metabolism
Ca2+ influx
What causes insulin exocytosis?
Intracellular Ca2+ increase
Outline the feedback control of insulin after a meal
Blood glucose concentration increases Insulin secretion stimulated Glucose uptake into cells by GLUT-4 Blood glucose concentration falls Stimulus for insulin secretion removed Blood insulin concentration falls
What do muscles and adipose tissue need for glucose entry to cells?
Insulin
Which transporter is stimulated by insulin?
GLUT4
What is the effect of insulin on GLUT4?
GLUT4 is a transporter stored within the cell
Insulin stimulates translocation to the plasma membrane
What concentrations of glucose are seen in diabetes patients?
High extracellular
Low intracellular
What does insulin promote?
Glucose disposal into muscle and adipose tissue
What enzymes does insulin activate in the liver?
Glucokinase Glycogen synthase Phosphofuctokinase Pyruvate dehydrogenase Acetyl CoA carboxylase Fatty acid synthase
What enzymes does insulin inhibit in the liver?
Glycogen phosphorylase
Glucose 6 phosphatase
What does insulin trigger in muscle?
Increased glucose uptake
Glycogen synthesis
Glycolysis
What enzymes does insulin activate in adipose tissue?
Pyruvate dehydrogenase
Acetyl CoA carboxylase
Lipoprotein lipase
What enzyme does insulin inhibit in adipose tissue?
Hormone sensitive TG lipase
What is utilised in the post absorptive state?
Glucose stores as none is being absorbed in the GI tract
What are the two ways energy is obtained in the post absorptive state?
Glucose-supplying reactions
Glucose-sparing reactions
What are glucose-sparing reactions?
Reactions which generate other energy substrates such as fatty acids and ketone bodies
Why are reactions essential during the post absorptive stage?
To preserve plasma glucose levels for brain function
In what two ways does the liver supply glucose?
Glycogenolysis
Gluconeogenesis
What controls glucose-supplying reactions?
Fall in insulin levels
Increase in hormones
What hormones are involved in glucose-supplying reactions?
Epinephrine
Glucagon
Cortisol
Growth hormone
What effect does epinephrine have?
Increases glycogen breakdown in muscles, adipocytes and the liver
What effect does glucagon have?
Increases glycogen breakdown and gluconeogenesis in the liver
What effect does cortisol have?
Increase gluconeogenesis in the liver and decreases glucose uptake
What does growth hormone do?
Decreases glucose uptake
How much ATP is produced by beta-oxidation?
34
Where are ketone bodies produced?
In the liver
Where do ketone bodies go?
From the liver to tissues for use in the Krebs cycle
What is a charecteristic of diabetes mellitus?
High blood sugar
What happens to the ratio of hormones in someone suffering from diabetes mellitus?
Increased ratio of hormones that increase blood sugar to insulin
(glucagon, adrenaline, growth hormone)
What is the cause of the shift in hormones?
Either insulin deficiency or insulin resistance
What is type 1 diabetes?
Young onset
Destruction of beta cells and loss of insulin production
Metabolic derangement by inability to utilise glucose
Switch to other fuels leads to marked weight loss
Also hyperlipidaemia and ketoacidosis
What is type 2 diabetes?
Prevalence increases with age
Insulin levels usually normal or high but with reduced action (resistance)
Treated with lifestyle changes, insulin stimulators or insulin
Less of an effect as some insulin action still present
Causes long-term damage due to high glucose levels and lipid abnormalities
What is the relationship between obesity and type 2 diabetes?
Obesity is present in 55% of sufferers
What happens in the liver of someone with diabetes?
Decreased glycogen synthesis
Increased glycogenolysis
What happens in adipose tissue of someone with diabetes?
Decreased glucose uptake
Increased lipolysis
What happens in the muscle tissue of someone with diabetes?
Increased extracellular
Breakdown of protein to amino acids as substrates for gluconeogenesis
What happens to levels of acetyl coA in diabetes sufferers?
Increased by the b-oxidation of fatty acids
What is the effect of increased acetyl coA levels?
Inhibits the Krebs cycle
Used for ketogenesis
What is the effect of high ketone levels?
Acidosis
What are clinical features of uncontrolled diabetes?
Polyuria Polydipsia Blurred vision Infections Weight loss Ketosis Confusion Coma
How is uncontrolled diabetes treated?
Rehydration with intravenous saline
Insulin injections
Monitor serum electrolytes
Treatment of symptoms such as infection
What is the impact of chronic diabetes?
Effects of high blood glucose
Thought to cause enzymatic glycation of proteins, altering their function
Sorbitol toxicity, sorbitol is produced from glucose by aldol reductase. Further glycation of tissues
What is retinopathy?
Growth of friable and poor quality new blood vessels in the retina
Macular edema
Leads to severe vision loss or blindness
What is nephropathy?
Damage to the kidney that can lead to chronic renal failure eventually requiring dialysis
Diabetes is the most common cause of adult kidney failure worldwide
What is neuropathy?
Abnormal and decreased sensation in the feet and then fingers and hands
With damaged blood vessels it can lead to diabetic foot (delayed wound healing, infection, gangrene)
What are the consequences of atherosclerosis?
Strokes
Heart attacks
Peripheral vascular disease
What is hyperlipidaemia?
Common in diabetes
High circulating fatty acid concentration
Atherogenic
What is hepatic steatosis?
Fatty liver
What causes hepatic steatosis?
Fatty acids taken up by liver and converted to triaglycerol
Deposited in the liver
What are long term treatments of diabetes?
Lipid lowering drugs Reduced blood pressure Aspirin Avoid smoking Diet Home monitoring Adjustment of tablets/insulin
Why is diabetes seen in cystic fibrosis patients?
CF gene creates CFTR protein
Blockage of pancreatic ducts
Ductal obstruction leads to pancreatic tissue distruction
