Flashcards in Glucose And Diabetes Deck (59):
What is cellular respiration?
Set of metabolic reactions in cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP) for use in energy requiring activities of cells
What are Anabolic reactions?
Generate complex molecules from smaller substrates
Suffix – genesis
What are catabolic reactions?
Break down complex molecules into smaller products
Release energy, which is transferred to ATP molecules
Suffix – lysis
What is catabolism used for?
40% energy released by catabolism is used for cellular functions
Rest is converted to heat which maintains body temp or is lost to environment
What are carbohydrates metabolised to?
Polysaccharide and disaccharide catabolised to monosaccharides: glucose, fructose and galactose
Shortly after absorption (small intestine) fructose and galactose converted to glucose
What is the preferred source of ATP?
What happens to glucose if ATP is needed immediately?
Glucose is Oxidised
What happens to glucose if ATP is not needed immediately?
Converted to glycogen for storage in liver cells & skeletal muscle fibers
If these full then liver converts glucose to triglycerides for storage in adipose tissue. Released when ATP required
What increases rate of facilitated diffusion of glucose?
Describe cellular respiration of glucose
1 glucose + 6O2 = 38 ATP + 6CO2 + 6H2O
What is the final electron acceptor in glucose respiration?
What are the key reactions in cellular respiration of glucose?
Formation of acetyl CoA
Electron transport chain
What are NAD+ and FAD?
Coenzymes: temporary carriers of atoms being removed or added to a substrate during the reaction
NAD+ accepts electrons and H+ ions, becomes reduced and forms NADH+H+, which can be oxidised to donate electrons and H+ ions to electron chain
What is glycolysis?
Glucose --> 2 x pyruvate + 2NADH + 2ATP
What are the 2 pathways of pyruvate?
Anaerobic: Lactate dehydrogenase --> lactate
Aerobic: Pyruvate dehydrogenase complex --> Acetyl coA + CO2
Describe the lactic acid pathway and why it happens
For glycolysis to continue, must be adequate amounts of NAD+ available, NADH has to be oxidised
If oxygen available this happens in the mitochondria and eventually donated to oxygen
If not enough oxygen NADH is oxidised in the cytosol donating
electrons to pyruvate and reduction of pyruvate by H+ forms lactic acid
Reaction is catalysed by lactic acid dehydrogenase
What respiration related factors are required for cells to survive?
As long as they make enough ATP
Lactic acid concentrations don’t rise too high
Which tissues cope best with lactic acid?
Skeletal muscle > cardiac muscle > brain
How do red blood cells undergo respiration?
Only anaerobic respiration
Spares the oxygen they are carrying
Describe the Formation of Acetyl CoA
Pyruvate enters mitochondria and is converted into 2-carbon fragment acetic acid (+CO2 – removed via blood and respiration)
Acetic acid + coenzyme A --> acetyl coenzyme A
Describe the Krebs cycle
Acetyl CoA (2 carbons) combines with oxaloacetic acid (4 carbons) to form citric acid (6 carbons)
Series of reactions citric acid is converted to oxaloacetic acid, join with a new acetylCoA and start again
For each cycle:
1 GTP produced (donates P to ADP to form 1 ATP)
3 NAD+ reduced to NADH
1 FAD is reduced to FADH2
What things other than pyruvic acid can pass into the Krebs cycle?
Describe the electron transport chain
NADH and FADH2 oxidised by transferring electrons to ETC
Free energy released during oxidation of NADH or FADH2 molecule by O2 sufficient to drive synthesis of ATP from ADP and Pi
Mitochondria maximise production of ATP by transferring electrons from NADH and FADH2 through series of electron carriers all but one of which are integral components of inner membrane
Step-by-step transfer of electrons allows free energy in NADH and FADH2 to be released in small increments
Oxidised forms (NAD+ and FAD) are regenerated and continue to shuttle electrons from Krebs cycle to electron chain
What is oxidation?
Loss of electrons from an atom or molecule as occurs when hydrogen is removed from the molecule or oxygen is added
Summarise cellular respiration
Glycolysis: Glucose --> 2ATP +2NADH
Krebs Cycle: 2 x acetyl CoA --> 2ATP + 6NADH + 2FADH2
Electron chain transport: 34ATP + 2NADH
Glucose = 38 ATP (anaerobic 2ATP, aerobic 36 ATP)
What is diabetes Mellitus?
Heterogeneous complex metabolic disorder characterised by elevated
blood glucose concentration secondary to resistance to action of insulin, insufficient insulin secretion, or both
Where can glucose supply come from?
Breakdown of glycogen stores (glycogenolysis)
Formation of glucose (gluconeogenesis)
What is the significance of the hydrophilicity of glucose?
Require specific transport proteins to move into cells
Name some glucose transporters
GLUT family: Facilitated diffusion, not energy dependent
GLUT 1,3 &4 movement at low glucose levels, GLUT 4 insulin dependent response in fat & muscles, GLUT 2 present on β-islet cells
SGLT (sodium dependent glucose transporter): Use sodium to move glucose against concentration gradient, SGLT1 – responsible for dietary uptake in intestines, SGLT2 – glucose re-absorption in kidney
What is Gluconeogenesis? And where does it happen?
Production of glucose from molecules (not carbohydrates)
Substrates are: Lactate, Glycerol (from fats), Glutamine and alanine (from protein)
Occurs in both liver and kidneys
What is glycogen and what does it do?
Energy storage molecule in humans, Multi-branched polysacharride
Primarily stored in liver and muscle cells
What hormones are involved in glucose homeostasis?
Major: Insulin, Glucagon
Minor: Catecholamines (Adrenaline, noradrenaline), Growth hormone, Cortisol, Free Fatty Acids, Incretins (GLP-1)
What is insulin?
51 amino acids peptide (protein) hormone
2 protein chains linked by disulphide bonds formed from cleavage of c peptide
Which cells produce insulin?
β-cells of Islets of Langerhans, Clusters of cells in pancreas
Provide endocrine function
What are the cells of the pancreas and what do they produce?
α-cells : glucagon
β-cells : insulin
δ-cells : somatostatin (Strong inhibitor of insulin & glucagon)
Describe the process of insulin release after glucose intake
Extracellular glucose transported into β -cell via GLUT-2
Glucose metabolised which increases ATP:ADP ratio in cell
Closure of ATP- K+ channels -> cell membrane depolarisation which leads to opening of voltage dependent Ca2+ channels and Ca2+ influx
Ca2+ influx leads to exocytosis of stored insulin vesicles
Describe the nature of insulin secretion
Insulin secretion occurs in two phases:
First phase: rapid onset and lasts ~ 10 minutes
Second phase: prolonged plateau as long as hyperglycaemia persists
Release of pre-docked and primed vesicles: First phase response
Only a portion of stored insulin is released, even under maximal stimulation
What are the actions of insulin?
GLUT4 stored in vesicles, Insulin promotes vesicle fusion & transporter insertion into cell walls, facilitates glucose transport into cells
Promotes activation of glycogen synthase
Promotes protein synthesis and inhibits protein breakdown
Promotes lipogenesis and inhibits lipolysis
Promotes mitogenesis (cell division)
What regulates glucagon secretion?
Blood Glu levels, Hypoglycaemia increases, Hyperglycaemia inhibits
Levels rise with fasting, exercise & physiological stresses
Suppressed by insulin secretion
Hypoglycaemia: loss of insulin secretion and suppression
Glucagon: earliest & crucial hormone responding to drops in blood glucose levels
What are the 5 roles of insulin?
What are the 5 roles of glucagon?
Where does most glucose entering the system come from during fasting?
80% of glucose entering system from liver~ 50% from glycogenolysis, ~ 50% from gluconeogenesis
Kidneys contribute, Contain little glycogen, so primarily gluconeogenesis, Output is comparable to the liver
In post absorptive state, is insulin or glucagon favoured? And what is occurring?
Insulin : Glucagon ratio favours glucagon
Primarily catabolic state
Production of precursors for gluconeogenesis and production of other fuels (e.g. ketones)
In the post prandial state, is insulin or glucagon favoured? And what is going on?
Insulin response to rising glucose levels
Acute exposure to free fatty acids increases basal and glucose stimulated insulin production
Insulin : Glucagon ratio favours insulin
Primarily anabolic state
What does the entero-insular axis do in the fed state?
L-cells of small intestine produce gastrointestinal insulinotropic
Glucagon-Like Peptides (GLP)
Gastric inhibitory peptide (GIP)
Augment insulin secretion in response to oral glucose load
What role does the autonomic nervous system play in glucose homeostasis?
Adrenaline release inhibits insulin and promotes glucagon secretion
ANS directly innervates pancreatic islets
Sympathetic neurons releasing NA, stimulate glucagon and inhibit insulin secretion
Parasympathetic neurons have opposite action
What role does cortisol and growth hormone play in glucose homeostasis?
Take several hours to have effect
Promote gluconeogenesis and inhibit glucose transport
Cortisol also directly inhibits insulin secretion
E.g. Prescribed steroids, syndromes of cortisol or GH excess
What are the 4 stages leading to diabetes?
Impaired fasting glycaemia
Impaired glucose tolerance
Describe Type 1 diabetes
Autoimmune destruction of β-cells, complete insulin deficiency
Rapid but can be a “honeymoon” period, Can only be treated with insulin, Accounts for 5-10% of all cases of diabetes
Typically seen in younger, lean patients
Associated with other autoimmune conditions E.g. thyroid disorders, coeliac disease
What might be presenting complaints and signs on examination of diabetes?
Polyuria: Hyperglycaemia -> glycosuria, Exceeds renal capacity to reabsorb glucose, inhibits concentrating ability of kidney
Polydipsia: Physiological response to dehydration, maintain fluid balance, High blood glucose stimulates thirst response directly
Weight loss: Unopposed lipolysis & proteolysis for gluconeogenesis
Hyperglycaemia: Loss of insulin secretion, Inability to uptake glucose into cells, Inability to store glucose as glycogen, Unopposed glucagon action, glygenolysis and gluconeogenesis
What is ketoacidosis and why can it occur in diabetes?
Ketones alternative energy source: fatty acid metabolism
Lead to acidaemia -> Diabetic ketoacidosis
Medical emergency seen in T1 DM. Presents with: shock from severe dehydration, High resp rate (blow off acid), Abdo pain, Can be first presentation in patient without known T1DM, preceded by other acute illness or insulin omission
What are 3 ketone bodies produced in diabetic ketoacidosis?
Acetone, acetoacetate and β-hydroxybutyrate
Describe type 2 diabetes
Insulin resistance and initially hyperinsulinaemia, Loss of first phase insulin response, Β-cell exhaustion occurs with time
Often asymptomatic at presentation
Associated with complex metabolic derangement
Central / visceral obesity, Dyslipidaemia, Other cardiac risk factors (e.g. HTN)
What are modifiable risk factors for type 2 diabetes?
Being overweight or obese, Body Mass Index > 25kg/m2
Central obesity (Waist circ.) >94cm/37in (men), >90cm/35in (south asian men), >80cm/31.5in (women)
Lack of physical activity / exercise
Poor diet, High saturated fat, Low fibre
Low socioeconomic status
What are non modifiable risk factors for type 2 diabetes Mellitus?
Age > 40 years, Age >25 years if south Asian origin
Ethnicity, Black African, South Asian
History of gestational diabetes or baby > 4.5kg (9.9lbs) at birth
Impaired glucose regulation, IGT, IFG (prediabetes)
History of mental health conditions or use of antipsychotic medication
History of hypertension, cardiovascular disease or stroke
Low birth weight
Polycystic ovarian syndrome
What is treatment for type 2 diabetes Mellitus?
Diet, exercise and lifestyle measures
Oral hypoglycaemic agents: Decrease hepatic gluconeogenesis – Biguanides (Metformin), Increase insulin secretion – Sulfonyureas, Reduce insulin resistance – Thiazolidinediones
Decrease carbohydrate absorption – α-glucosidase inhibitor
Prevent breakdown of GLP – DPP-4 inhibitors
Promote glycosuria – SGLT2 inhibitors
Injectable agents: GLP-1 analogues, Insulin
How does Metformin work?
Decrease hepatic gluconeogenesis
What can be alternative causes of diabetes?