1. Hormonal control of circulating nutrients Overview: The need for glucose and nutrient homeostasis Interchange of nutrients / fuel stores Insulin:secretion mechanism of action (resistance) effects: CHO, fat protein special sites Counter regulatory hormones Glucagon: control of secretion effects: CHO, fat, protein Cortisol Adrenalin Growth hormone Balance

2. Nutrient availability in blood Time Insulin & glucagon from pancreatic islets glucagon insulin with insulin & glucagon this is converted to: Supply of nutrients constant Balance between insulin : glucagon (+ others) Converts irregular food supply into a near constant supply of nutrients

3. Homeostasis Blood glucose concentrations 3  5 mmol/L Consequences of hypoglycemia (  blood glucose) CNS: (unable to use fatty acids for energy) disorientation, hunger, decreased consciousness convulsions coma death Early warning – features due to adrenalin release, sympathetic stimulation eg fast pulse, tremor, sweating

4. Hyperglycemia (  blood glucose)  urine flow, dehydration intracellular dehydration eg CNS Long term: glycation of proteins  functional complications

5. Nutrients in dietBloodstream Endogenous nutrient stores Eating: Nutrients in dietBloodstream Insulin released Uptake & storage of nutrients Endogenous nutrient stores Fasting: Nutrients in dietBloodstream  Glucagon + others Available for cells Endogenous nutrient stores

6. Fasting (  insulin,  glucagon +) Liver GlycogenGlucose-6-PGlucose Pyruvic acid Acetyl CoA Ketone bodies Fatty acids Adipose tissue Amino acids Skeletal muscle

7. Fuel stores Relative amounts of energy stored as glycogen (1800kcal), vs fat (140,000kcal) and protein (41,000kcal). Glycogen  glucose (but only liver able to release stored glucose  blood) Inability to convert fatty acids into glucose – but  the oxidation of fatty acids inhibits the oxidation of glucose so glucose is not wastefully oxidised  glycerol released from lipolysis is converted into glucose by gluconeogenesis in the liver  ketone bodies formed from fat oxidation can be used as an alternate to glucose by many tissues Protein  amino acids  glucose via gluconeogenesis

8. Stimulators of insulin secretion  Glucose concentration  Amino acid concentration Food intake— GI hormones — parasympathetic stimulation

9.  Blood glucose concentration Major control Islet  cells Insulin secretion Blood glucose Blood fatty acids Blood amino acids Protein synthesis Fuel storage Gastrointestinal hormones Food intake Parasympathetic stimulation Blood amino acid concentration Sympathetic stimulation (and epinepherine) Somatostatin Phenytoin Thiazide diuretics

10. Golgi ---------- converting enzmes “Folded” proinsulin Secretion Granule

11. Plasma insulin as a function of time following a rapid increase in blood glucose to 3-fold normal

12. Insulin release Portal circulation Intestine liver Liver exposed to higher conc of insulin (and glucagon) than peripheral tissues

13. Insulin Action  Tyrosine kinase Response depends on adequate insulin, normal receptors, normal cellular responsiveness

14. Insulin — anabolic  Uptake  Storage  Breakdown of stored nutrients

15. Insulin effects on Glucose  Uptake esp. muscle, fat tissue: glucose transporter  cell membrane facilated diffusion  Glycogen synthesis  Glycogenolysis

16. Insulin effects on Fats  Uptake: (  low density lipoprotein receptor)  Fat as triglyceride  Fat breakdown

17. Insulin effects on Proteins  Amino acid uptake  Protein synthesis  Protein breakdown

18. Special sites: Liver Glycogen Liver Gluconeogenesis glucose Also  ketone production BloodstreamCells Insulin effects on

19. Special sites cont: Kidney – insulin has no effect on glucose transport. Glucose reabsorbed Transport max. Filtered  blood glucose conc. If excess glucose filtered. Not all reabsorbed Urine

20. Glucose = osmotic diuretic  water reabsorption Large volume sweet urine = Diabetes mellitus polyuria polydipsia

21. Special sites: Brain – absolutely depends on glucose mostly glucose transport is insulin independent, except satiety centre Intestine – glucose absorption is insulin independent Muscle – glucose uptake with exercise is insulin independent

22. Fasting: releases “counter regulatory hormones” Glucagon (pancreatic islets) Adrenalin Cortisol Growth hormone * All antagonize insulin actions Also released by stress * growth hormone does not protein breakdown

23. Glucagon (  cells) release stimulated by:  Glucose  Fatty acids  Amino acids (high protein, low CHO meal)

24. Catabolic:  release stored nutrients CHO:  Glycogen breakdown  Gluconeogenesis (liver) Amino acids: Protein breakdown  liver Fats: Lipolysis Ketogenesis (liver)

26. Metabolism  Insulin  Glucagon  Insulin / Glucagon ratio Formation of glycogen, fat and protein Blood  Glucose  Amino acids  Fatty acids  Ketone bodies  Insulin  Glucagon  Insulin / Glucagon ratio Hydrolysis of glycogen, fat and protein + Gluconeogenesis and ketogenesis Blood  Glucose  Amino acids  Fatty acids  Ketone bodies Absorption of meal (  glucose) Fasting (  glucose)

27. Summary Diet vs endogenous stored substrates Uptake & storage vs release Insulin anabolic Glucagon (cortisol, adrenalin)catabolic Growth hormone catabolic & anabolic Balance between insulin & counter regulatory hormones