20- Metabolic & Endocrine Control During Exercise And Pregnancy

Question 1

• name some fuel sources that are normally available in blood?
• name some fuel sources that are only available under special conditions?
• describe what happens after feeding and time periods for each step.

Answer 1

• normally available=1)glucose-the preferred fuel, needed exclusively ie brain cells, cells of lens of eye, RBCs, neutrophils. 2)fatty acids=used by most other cells, stored as TAGs in adipose.
• special circumstances=1)aa’s-some muscle protein broken down, converted to glucose or ketone bodies. 2)ketone bodies-mainly from FAs, used when glucose v low, brain uses it instead of glucose. 3)lactate-product of anaerobic metabolism, liver converts back to glucose or it’s used as fuel for Krebs in heart.
• feeding supplies glucose & fat available from gut for ~2hrs, glycogen is made during this time (glycogenesis) + increase fat stores, after ~2-10hrs glucose and fats are no longer absorbed so glucose maintained by glycogenolysis + FAs released from stores to preserve glucose for brain. After ~8-10hrs of fasting the glycogen are depleted new glucose is made from aa’s, glycerol and lactate by gluconeogenesis. After this is STARVATION= when FAs are metabolised to make ketone bodies + brain metabolises ketone bodies and reduces its need for glucose.

Question 2

• name the main anabolic hormones and it’s job. Name the main catabolic hormones and their general role.
• name what processes insulin inhibits and what processes it promotes.
• briefly describe the effects of feeding and the effects of fasting.

Answer 2

• anabolic=mainly insulin (also growth hormone), promote fuel storage, if there’s a lack of insulin it goes into the catabolic state. Catabolic=promote release from stores & utilisation, ie glucagon, adrenaline, cortisol, growth hormone, THs.
• insulin inhibits(bc gluc conc is high so don’t need to break down stores) =gluconeogenesis, glycogenolysis, lipolysis, ketogenesis, proteolysis. Insulin promotes(gluc conc high so need to store it)=glucose uptake into muscle and adipose (GLUT4), glycolysis, glycogen & protein synthesis.
• effects of feeding=increase in blood glucose stimulates pancreas to release insulin causing: storage of glucose as glycogen, amino acid uptake + protein synthesis, promotes lipogenesis + storage of FA.
• effects of fasting=blood glucose falls & insulin secretion is limited. Stimulates glucagon which stimulates:glycogenolysis, lipolysis, gluconeogenesis (to provide brain w glucose).

Question 3

• describe the events during starvation from release of glucagon & cortisol to death.
• what is refeeding syndrome and why is it important.
• in pregnancy, how much does the mothers weight change and when does the foetus grow the most?

Answer 3

• cortisol and glucagon are released and they stimulate breakdown of protein and fat & gluconeogenesis. Reduction in insulin & anti-insulin effects of cortisol means cells preferentially use FAs, glycerol from FAs is used first for gluconeogenesis. Liver produces ketone bodies which the brain uses to limit need to aa’s. Kidneys then start to contribute in gluconeogenesis. When glycerol runs out protein must be used for gluconeogenesis so muscle mass decreases. Death is usually from loss of muscle (eg from lungs therefore more infection)
• refeeding syndrome=patient is malnourished and their urea cycle has been down regulated by their body due to lack of protein intake so if given protein too fast can lead to ammonia poisoning.
• net weight gain of around 8kg by end of pregnancy, most foetal growth is in the last 1/3 of pregnancy (28weeks onwards).

Question 4

• describe the 2 main phases of metabolic adaptation during pregnancy. mention insulin/anti-insulin ratio changes
• describe the main transporter by which glucose is transporters from mother through the placenta and by which mechanism it happens.
• why is the placenta described as an aggressive parasite? What do its adrenal glands constitute? Name the range of proteins the placenta secretes to control the maternal hypothalamic pituitary axis.

Answer 4

-1)anabolic phase=EARLY pregnancy, preparatory increase in maternal nutrient stores (esp adipose) for foetal growth, birth, lactation, increase in fat stores, increase insulin/anti-insulin ratio, a small increase in level of insulin sensitivity(v quickly senses increase in gluc and takes it to be stored efficiently eg glycogenesis). -2)catabolic phase=LATE pregnancy, decreased insulin sensitivity (blood gluc will increase and stay high so maternal glucose is high for foetus and free FAs are available for mother to use mainly. G
Delayed maternal disposal of nutrients after meals. Maternal insulin levels increase but anti-insulin hormones are produced by the fetal-placental unit even faster therefore decrease in insulin/anti-insulin ratio.(we want gluc to stay in blood to be taken up by placenta not be stored by mother)
-glucose is the main fuel for foetus, main transporter is GLUT1, via simple diffusion down a concentration gradient.
-parasite bc it controls mothers metabolism to ensure its survival. It’s adrenal glands and liver form a new endocrine entity (called fetoplacental unit). Placenta secretes=pituitary like hormones (eg ACTH, hCG-human chorionic gonadotropin)and hypothalamic like releasing hormones (eg CRH, GnRH, GHRH)

Question 5

• name the 2 important placental steroid hormones.
• name the main anti-insulin hormone describe how it works and its effect.
• what is blood gluc like overall in late pregnancy & why.
• how do the pancreatic beta cells respond to pregnancy?

Answer 5

• oestriol and progesterone
• corticotropin releasing hormone (CRH) increased 100 fold, causes maternal, anterior pituitary to become desensitised resulting in less cortisol and ACTH secreted so increase in blood glucose not sensed as much.This results in a transient hyperglycaemia after meals bc of increased insulin resistance.
• overall, late pregnancy has blood glucose ~10% lower since insulin levels are higher when fasting (so foetus can take gluc from blood-this is why they can get hypo at night & between meals as foetus continually takes gluc from mothers blood)
• there’s increased appetite in pregnancy so more gluc is ingested, oestrogen + progesterone increases sensitivity of beta cells leading to hyperplasia and hypertrophy of them, this causes increased insulin synthesis & secretion. *if B cells don’t respond to increased glucose it may be severely elevated (gestational diabetes)

Question 6

• what is gestational diabetes? give 3 known causes.
• give some clinical implications of gestational diabetes.
• what is the reasoning why some women may develop gestational diabetes but some women do not? why is risk increased w age?

Answer 6

• gestational diabetes=disease in which the pancreatic B cells don’t produce enough insulin to meet increased demand in late pregnancy. Causes=B cell dysfunction due to obesity & chronic insulin resistance (ie ‘evolving’ T2DM), genetic susceptibility, autoantibodies w similar characteristics to T1DM -rare.
• implications=increased incidence of miscarriage, foetal macrosomia (big baby) therefore can lead to shoulder dystocia (shoulders get stuck during birth), associated w pre-eclampsia (high BP & protein in urine during preg).
• depends on starting point of insulin resistance before pregnancy: women will have a spike during pregnancy in insulin resistance, those w higher resistance already their spike will reach T2DM level, those w low IR their spike will not. IR increases w age as fat:lean body mass ratio increases.

Question 7

• give RFs and management for gestational diabetes.
• what does the metabolic response to exercise need to ensure?
• what does the metabolic response to exercise depend on?

Answer 7

• RFs=age over 25 years, BMI above 25, Asian, black more common. Manage=dietary modifications, insulin injection if persistent hyper.
• increased demands of skeletal and cardiac muscle are met by mobilisation stores, minimal disturbance to metabolic homeostasis, gluc supply to brain is maintained.
• 1)type of exercise (muscles used), 2)intensity and duration, 3)physical condition & nutritional state of person.

Question 8

• ATP stores are used in exercise but can rapidly run out. What stores in the muscles are used instead and how long do they last?
• how does the liver control blood glucose during exercise?
• are FAs good as fuels and what environment can they only be used in?

Answer 8

-after ATP stores run out, muscle creatine phosphate stores rapidly replenish ATP (creatine phosphate + ADP ->creatine and phosphate)creatinine is diff and us measured clinically as a measure of muscle mass or kidney function. This store only lasts for ~5secs.
After this runs out, muscle glycogen stores can supply glucose for ~2mins of intensive exercise (glycogen via glycogenolysis converted to gluc6P which enters glycolysis to make pyruvate which then enters Krebs to make ATP (aerobic only)
-in exercise, there’s increased blood gluc due to glycogenolysis & gluconeogenesis. Liver recycled lactate produced by anaerobic metabolism(Cori cycle), muscle takes up gluc via GLUT4 & GLUT1. Rate of gluc production by liver is still insufficient.
-yes, slow release from adipose, low rate of ATP production but high capacity for sustained production. Only used in aerobic bc FAs must be oxidised.

Question 9

• describe the differences in ATP supply during a 100m sprint, 1500m middle distance & marathon.
• describe how 4 main hormones change during the course of running a marathon.

Answer 9

• 100m sprint=high intensity and short, can’t deliver enough O2 in time, when ATP stores are used must create ATP anaerobically which also produced lactate & buildup in H+ causes fatigue, can’t deliver extra gluc in time so uses muscle glycogen store. -1500m middle distance=medium intensity, can deliver some O2 to muscles to make their ATP but 40% still anaerobic- 3 phases to race=start uses creatine phosphate and anaerobic glycogen, middle is steady so uses O2 to make ATP from muscle glycogen, end is sprint and uses anaerobic glycogen metabolism producing lactate. -marathon=low intensity and long duration, 95% aerobic, uses muscle + liver glycogen and FAs to make ATP.
• 1)insulin levels fall slowly(secretion is inhibited by adrenaline). 2)glucagon levels rise (stimulating glycogenolysis- glycogen phosphorylase, gluconeogenesis-F16BP, lipolysis-hormone sensitive lipase). 3)Adrenaline and GH rise rapidly (adrenaline stimulates glycogenolysis & lipolysis, GH stimulates gluconeogenesis). 4)Cortisol rises slowly(stimulates gluconeogenesis).

Question 10

-give 5 benefits of exercise.

Answer 10

-body composition changes (increase muscle, decrease fat), glucose tolerance improves, blood TAGs decrease (LDLs and VLDLs decrease, HDLs increase), blood pressure falls, feeling of well-being.