13 - Metabolic challenges to homeostasis

Question 1

lysis

Answer 1

break down

Question 2

genesis

Answer 2

make new

Question 3

glyco

Answer 3

glycogen

Question 4

gluco

Answer 4

glucose

Question 5

glycogenolysis

Answer 5

conversion of glycogen to glucose

Question 6

gluconeogenesis

Answer 6

production of new glucose (from a few amino acids, glycerol, lactic acid etc)

Question 7

glycogenesis

Answer 7

storage of glucose as glycogen

Question 8

anabolism

Answer 8

synthesis

Question 9

catabolism

Answer 9

breakdown

Question 10

effects of insulin (3)

Answer 10

• 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)

Question 11

effects of glucagon (3)

Answer 11

• promotes catabolism
  1. increased liver glycogen breakdown -> glucose (glycogenolysis)
  2. increased glucose production (glucogenesis)
  3. lipid break down (lipolysis)

Question 12

where does insulin act?

Answer 12

many sites, predominantly skeletal muscle, liver and adipose tissue

Question 13

insulin action

Answer 13

promotes insertion of glutamate transporter GLUT4 into membrane (e.g. skeletal muscle). GLUT4 transporters facilitate glucose uptake down concentration gradient

Question 14

local glucose sensing

Answer 14

sensed by pancreatic a/B cells (dependant on cellular ADP:ATP levels)

Question 15

central glucose sensing

Answer 15

sensed by glucose-sensitive neurons in the hypothalamic nuclei

Question 16

indirect glucose sensing

Answer 16

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

Question 17

plasma glucose response to eating (a meal) (2)

Answer 17

1. plasma glucose and insulin rise rapidly after a meal over course of 1-2 hours
2. plasma glucose decline followed by insulin
   - allows dynamic bodily response to move towards anabolism

Question 18

5 phases of glucose metabolism (5)

Answer 18

1. fed state (glucose acquired from dietary source)
2. early fasting: glycogenolysis (glucose acquired by lysing glycogen stores in liver)
3. late fasting: gluconeogenesis (glucose synthesised from sugars, lipids and some amino acids)
4. early starvation: fatty acid oxidation becomes dominant, ketone bodies also used in TCA/Krebs cycle
5. late starvation: fatty acid and ketone bodies used to exhaustion, amino acids from muscle proteins then metabolised

Question 19

how are glucose reserves allocated in late stages (4/5) of glucose metabolism?

Answer 19

last remaining glucose reserves used in brain, RBCs and kidneys (rest of body moves to fatty acids/ketone bodies)

Question 20

diabetes mellitus

Answer 20

metabolic disorder: genetic and environmental risks, defects in insulin signalling, elevated blood glucose, glucosuria (glucose in urine)

Question 21

type 1 diabetes mellitus (2)

Answer 21

1. aggressive autoimmune loss of pancreatic B cells, usually early onset
2. very low insulin levels, requires replacement

Question 22

type 2 diabetes mellitus (3)

Answer 22

1. resistance to insulin, can involve high circulating insulin (hyperinsulinemia)
2. progressive loss of pancreatic B cells
3. usually later onset, usually contributed by diabetogenic diet and genetic risk

Question 23

metabolic effects of diabetes mellitus (type 1/2) (6)

Answer 23

1. decreased cellular uptake of glucose - poor cellular use of glucose
2. increased catabolism/ decreased anabolism
3. increased gluconeogenesis
4. increased glycogenolysis
5. increased protein and lipid breakdown
6. increased protein glycation (sugar molecule binding to protein)

Question 24

protein glycation example (2)

Answer 24

1. sugar molecule binding to proteins
2. e.g. haemoglobin - associated with vascular, renal and nerve inflammatory damage

Question 25

net metabolic effect of diabetes mellitus

Answer 25

increased circulating plasma glucose and impaired normal metabolic function

Question 26

diabetic ketoacidosis

Answer 26

decreased blood pH due to accumulation of acidic ketone byproducts

Question 27

cause of diabetic ketoacidosis

Answer 27

ketone bodies metabolised to enter krebs cycle when glucose uptake is poor

Question 28

symptoms of diabetic ketoacidosis (3)

Answer 28

1. extreme hunger/thirst 2. dizziness/ delirium 3. risk of death without treatment

Question 29

insulin replacement therapy for type 1/2 diabetes (2)

Answer 29

1. type 1 = lifelong 2. type 2 = generally late-stage

Question 30

treatments for diabetes mellitus (4)

Answer 30

1. insulin replacement therapy 2. strict diet management 3. metformin (reduces liver gluconeogenesis) 4. SGLT inhibitors (inhibit glucose absorption in intestines (SGLT1)/kidneys (SGLT2) - overall aim = restore homeostatic control of glucose

Question 31

glucagon-like peptide 1 (2)

Answer 31

1. hormone (many different actions, similar to insulin) 2. receptors for GLP1 in brain decrease food intake

Question 32

ozempic

Answer 32

GLP1 receptor agonist (mimics effects)

Question 33

ozempic effects (3)

Answer 33

1. decreases appetite and food seeking 2. increased insulin signalling 3. significant weight loss in clinical trials

Question 34

cholecystokinin (3)

Answer 34

1. hormone, released in multiple sites (including small intestine), stimulates pancreatic juice/bile secretions 2. signals satiety via parasympathetic vagus nerve 3. CCK administration decreases food intake in rats

Question 35

cholecystokinin signalling via vagus nerve (2)

Answer 35

1. appetite suppressing effect reduced by cutting vagus nerve (vagotomy) 2. suggests CCK signalling to PNS important for controlling feeding

Question 36

set point model for energy homeostasis and feeding (4)

Answer 36

1. set point: weight may have some form of set point signal 2. comparator: compares set point signal to actual signal, affected by 'incentive' 3. error signal: difference between set point and actual weight activates negative feedback response via endocrine, autonomic or behavioural systems 4. controlled variables and feedback detectors: changes such as blood glucose then fed back