Carbohydrate metabolism and control of blood glucose Flashcards
What is the enzyme required to make free glucose needed for glycolysis
Glucose 6-phosphatase
Outline the metabolism of carbohydrates
- Occurs in the liver
- Fructose and galactose are converted into glucose
- Glucose is then converted to pyruvate via glycolysis
- enters TCA cycle then used in oxidative phosphorylation
What are the processes by which fat and amino acids can be converted to glucose
Fat = Beta oxidation
Amino Acids = gluconeogenesis
How is glucose transported across cell membranes
Via facilitated diffusion so requires transporter proteins and rate of diffusion will reach a plateau
Where are the different glucose transporters located and what are their functions
GLUT1 - most tissues (brain and blood cells) controls basal glucose uptake
GLUT2 - Liver, kidney, pancreatic Beta cells, used to remove excess glucose from blood and control insulin release
GLUT3 - CNS, controls basal glucose uptake
GLUT4 - Skeletal muscle and adipose tissue, Insulin and exercise increase GLUT4 at the plasma membrane
SGLT - GI tract, different involves active sodium-glucose transporter
structure of insulin and where is it produced?
- Polypeptide made of two amino acid chains connected by disulphide bridges
- Pancreatic Beta cells in the islets of Langerhans produce the insulin
- production is stimulated by high glucose
- degraded by insulinase
what reaction does glucokinase catalyse
phosphorylates glucose to form glucose 6-phosphate
What is the mechanism of insulin secretion?
1) glucose enters GLUT2 receptor of beta-cell
2) once in the cell through the TCA cycle produces ATP
3) ATP closes the potassium channels which depolarises the cell resulting in the opening of calcium channels
4) Calcium entry into the cell is the insulin secretion signal
5) granules of insulin from ER, Golgi apparatus and free granules exocytose and enter bloodstream
what are the drugs and hormones regulating insulin and where do they act?
1) Sulfonylureas close the potassium channels without needing glucose production of ATP
2) GLP-1 (Glucagon-like peptide) acts as an insulin secretion signal instead of calcium
3) Somatostatin and norepinephrine inhibit insulin release from Islets
Factors regulating insulin secretion
1) Main control is blood glucose concentration, High = insulin produced
2) High blood amino acid concentration = insulin produced as AA’s are insulin secretion signal
3) GI hormones increase insulin e.g. gastrin CCK and GIP
4) parasympathetic stimulation increases insulin
5) sympathetic stimulation decreases insulin production
Metabolic actions of insulin
Adipose tissue: dec lipolysis, inc lipogenesis, inc glucose uptake
Striated muscle: inc glycogen synthesis, inc glucose uptake by inc GLUT4, inc protein synthesis
Liver: inc glycogen synthesis by increasing glycogen synthase, inc lipogenesis, dec gluconeogenesis, inc glucose uptake by increasing glucokinase
What enzymes are required for glycogen breakdown and synthesis
Glycogen phosphorylase (breakdown) Glycogen synthetase (synthesis)
which hormones raise glucose
glucagon
adrenaline/noradrenaline - Alpha inc glycogenolysis (liver) and Beta inc lipolysis
cortisol - inc lipolysis and gluconeogenesis, dec glucose uptake
growth hormone - inc gluconeogenesis (liver) and lipolysis (adipose tissue), dec glucose uptake (muscle)
What do Islets of Langerhan secrete
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
How does glucagon stimulate glycogen breakdown
Glucagon binds to G-protein coupled receptor which creates a signalling cascade and amplification to increase cAMP and PKA (protein kinase A) which stimulate glycogen phosphorylase promoting glycogenolysis (glycogen breakdown into glucose)
What factors increase/decrease glucagon secretion
- Decreased blood glucose and increased circulating amino acids (more gluconeogenesis) increase glucagon secretion
- exercise increase glucagon
- somatostatin inhibits glucagon secretion, somatostatin suppresses metabolism so nutrients can be used for longer (not broken down)
Differences between type 1 and 2 diabetes?
1) insulin-dependent, Beta-cell dysfunction, cause (viral infection, autoimmune, hereditary) onset 14
2) non-insulin dependant, insulin resistance, obesity-related and onset adult
in Type one no insulin is being produced in type two insulin is not effective in cells
Effects of hyperglycaemia
Tired, hungry, thirsty, frequent urination, weight loss, blurry vision, wounds won’t heal and tingly feet and hands
Which transporter proteins are needed to transport glucose back into blood in the nephron
SGLT 1 or 2 transports sodium and glucose out of the tubule into the cell then GLUT2 transports back into the blood (sodium-potassium pump transports the sodium back into the blood)
If glucose concentration is too high proximal tubule can become overwhelmed and glucose can be excreted
Which drugs decrease renal glucose reabsorption
Gliflozins helps decrease blood glucose levels
What are polyuria and polydipsia
Polyuria is excessive urination
polydipsia is excessive water consumption
both can result from hypoglycaemia
Impacts of glucotoxicity
Glucose reacts with and alters proteins, these proteins then cause problems in the cell which can eventually lead to tissue damage. Cause: atypical cellular messaging, chronic inflammation, Beta-cell dysfunction and endothelial dysfunction
What causes metabolic acidosis and diabetic ketoacidosis
Lack of insulin which normally inhibits lipolysis means more fats are broken down into fatty acids and glycerol. Fatty acids undergo Beta-oxidation in the liver to create keto acids. Ketones decrease blood PH causing metabolic acidosis. H+ can also disrupt intracellular potassium causing hyperkalaemia
What symptoms of hyperglycaemia are caused by increased depletion of body protein and fat
- Weight loss
- increased appetite
- tissue wastage
- asthenia (lack of energy)
depletion is due to energy needing to be produced from these sources as no insulin
Complications of diabetes
- Major CVD risk factor
- Retinopathy
- Stroke
- Nephropathy (damage to kidneys)
- Neuropathy (damage to nerves)
How is Diabetes diagnosed?
Check:
- Urinary glucose
- Fasting blood glucose
- Fasting plasma glucose
- Glucose tolerance
- Presence of ketoacidosis
