13 - Metabolic challenges to homeostasis Flashcards
lysis
break down
genesis
make new
glyco
glycogen
gluco
glucose
glycogenolysis
conversion of glycogen to glucose
gluconeogenesis
production of new glucose (from a few amino acids, glycerol, lactic acid etc)
glycogenesis
storage of glucose as glycogen
anabolism
synthesis
catabolism
breakdown
effects of insulin (3)
- promotes anabolism
1. increased glucose uptake
2. increased conversion of glucose to glycogen (glycogenesis)
3. increased protein and lipid synthesis (excess glucose beyond glycogen storage goes to adipose storage)
effects of glucagon (3)
- promotes catabolism
1. increased liver glycogen breakdown -> glucose (glycogenolysis)
2. increased glucose production (glucogenesis)
3. lipid break down (lipolysis)
where does insulin act?
many sites, predominantly skeletal muscle, liver and adipose tissue
insulin action
promotes insertion of glutamate transporter GLUT4 into membrane (e.g. skeletal muscle). GLUT4 transporters facilitate glucose uptake down concentration gradient
local glucose sensing
sensed by pancreatic a/B cells (dependant on cellular ADP:ATP levels)
central glucose sensing
sensed by glucose-sensitive neurons in the hypothalamic nuclei
indirect glucose sensing
sensed indirectly from hormonal signals in digestive system (e.g. small intestine and liver)
- signals sent to vagus nerve or hypothalamus and brain stem via blood
plasma glucose response to eating (a meal) (2)
- plasma glucose and insulin rise rapidly after a meal over course of 1-2 hours
- plasma glucose decline followed by insulin
- allows dynamic bodily response to move towards anabolism
5 phases of glucose metabolism (5)
- fed state (glucose acquired from dietary source)
- early fasting: glycogenolysis (glucose acquired by lysing glycogen stores in liver)
- late fasting: gluconeogenesis (glucose synthesised from sugars, lipids and some amino acids)
- early starvation: fatty acid oxidation becomes dominant, ketone bodies also used in TCA/Krebs cycle
- late starvation: fatty acid and ketone bodies used to exhaustion, amino acids from muscle proteins then metabolised
how are glucose reserves allocated in late stages (4/5) of glucose metabolism?
last remaining glucose reserves used in brain, RBCs and kidneys (rest of body moves to fatty acids/ketone bodies)
diabetes mellitus
metabolic disorder: genetic and environmental risks, defects in insulin signalling, elevated blood glucose, glucosuria (glucose in urine)
type 1 diabetes mellitus (2)
- aggressive autoimmune loss of pancreatic B cells, usually early onset
- very low insulin levels, requires replacement
type 2 diabetes mellitus (3)
- resistance to insulin, can involve high circulating insulin (hyperinsulinemia)
- progressive loss of pancreatic B cells
- usually later onset, usually contributed by diabetogenic diet and genetic risk
metabolic effects of diabetes mellitus (type 1/2) (6)
- decreased cellular uptake of glucose - poor cellular use of glucose
- increased catabolism/ decreased anabolism
- increased gluconeogenesis
- increased glycogenolysis
- increased protein and lipid breakdown
- increased protein glycation (sugar molecule binding to protein)
protein glycation example (2)
- sugar molecule binding to proteins
- e.g. haemoglobin - associated with vascular, renal and nerve inflammatory damage
net metabolic effect of diabetes mellitus
increased circulating plasma glucose and impaired normal metabolic function
diabetic ketoacidosis
decreased blood pH due to accumulation of acidic ketone byproducts
cause of diabetic ketoacidosis
ketone bodies metabolised to enter krebs cycle when glucose uptake is poor
symptoms of diabetic ketoacidosis (3)
- extreme hunger/thirst
- dizziness/ delirium
- risk of death without treatment
insulin replacement therapy for type 1/2 diabetes (2)
- type 1 = lifelong
- type 2 = generally late-stage
treatments for diabetes mellitus (4)
- insulin replacement therapy
- strict diet management
- metformin (reduces liver gluconeogenesis)
- SGLT inhibitors (inhibit glucose absorption in intestines (SGLT1)/kidneys (SGLT2)
- overall aim = restore homeostatic control of glucose
glucagon-like peptide 1 (2)
- hormone (many different actions, similar to insulin)
- receptors for GLP1 in brain decrease food intake
ozempic
GLP1 receptor agonist (mimics effects)
ozempic effects (3)
- decreases appetite and food seeking
- increased insulin signalling
- significant weight loss in clinical trials
cholecystokinin (3)
- hormone, released in multiple sites (including small intestine), stimulates pancreatic juice/bile secretions
- signals satiety via parasympathetic vagus nerve
- CCK administration decreases food intake in rats
cholecystokinin signalling via vagus nerve (2)
- appetite suppressing effect reduced by cutting vagus nerve (vagotomy)
- suggests CCK signalling to PNS important for controlling feeding
set point model for energy homeostasis and feeding (4)
- set point: weight may have some form of set point signal
- comparator: compares set point signal to actual signal, affected by ‘incentive’
- error signal: difference between set point and actual weight activates negative feedback response via endocrine, autonomic or behavioural systems
- controlled variables and feedback detectors: changes such as blood glucose then fed back
