The slides explain about blood glucose regulation, glucose homeostasis, factors regulating and under Special Circumstances. Factors regulating Blood glucose level include the hormonal and non-hormonal.

1. BLOOD GLUCOSE REGULATION

2. OUTLINE
• Why to know?
• Different Terms used..
• Normal levels..
• What should we study in BGR?
• Factors regulating…
• Glucose regulation in special situations…

3. BASIC PRINCIPLES
• Humans have a constant requirement for energy but eat only
intermittently.
• Ingestion of food in excess of the immediate caloric needs of
our vital organs.
• Store the extra calories
• Hepatic and muscle: glycogen,
• Adipose tissue: triglyceride,
• Tissue :protein.
• Fuel reservoirs used when needed.

5. • The two principal circulating fuels,
• Glucose (glycogen)
• Free fatty acids (triglycerides)
• The largest reservoir of glycogen
• Liver (10 gm/100 gm)
• Skeletal muscle (1-2 gm/100 gm)
• But liver glycogen provides free glucose during fasting.
• Provides glucose for about 16 hrs-18 hrs of fasting.
• After that fatty acid oxidation meets energy requirement.

6. WHY TO KNOW BGR…..
• The brain has a continuous need for fuel but stores almost
no energy as glycogen or fat.
• Instead, it uses glucose derived from the liver either directly
from glycogen or indirectly from other fuel reservoirs
through gluconeogenesis.
• The brain does not use FFAs directly.
• Not capable of gluconeogenesis.

7. TERMS USED IN BLOOD
GLUCOSE MONITORING…
• FASTING BLOOD GLUCOSE
• When measured after 12 hours over night fast
• POST-PRANDIAL
• Measured 2 hours after meal
• Prandium in Latin means meal or repast
• RANDOM BLOOD GLUCOSE
• Measured without any prior preperations

8. NORMAL VALUES*
• FASTING GLUCOSE
 < 100 mg/dL
 < 6.1 mmol/L
• POST PRANDIAL (2 HRS AFTER EATING )
 < 140 mg/dL
 < 7.8 mmol/L
• RANDOM
 70 - 140 mg/dL
* AMERICAN DIABETIC ASSOCIATION

9. WHAT TO KNOW…
• Five phases of glucose homeostasis
• Glucose homeostasis
• Hormonal
• Non-hormonal
• Details of hormonal regulation

10. FIVE PHASES OF GLUCOSE
HOMEOSTASIS
• Based on the source and quantity of glucose
entering the circulation.
I
• well fed state (< 4 hrs)
II
• hepatic glycogenolysis(16 hrs)
III
• hepatic gluconeogenesis (<40 hrs)
IV
• gluconeogenesis & ketogenesis (24
days)
V •ketogenesis mainly (40 days)

13. PHASE I
• First few hours after a carbohydrate meal, glucose meets
metabolic needs of the brain and other organs.
• Excess of these is used to rebuild fuel reservoirs.
• Plasma insulin levels are high, plasma glucagon levels are low,
• Glycogen synthesis is stimulated in liver and muscle.

15. PHASE II(EARLY
STARVATION)
• With plasma insulin decrease and increase in plasma
glucagon that accompany an overnight fast, fuel
homeostasis shifts from energy storage to energy
production
• At this stage, glucose is derived principally from the
breakdown of liver glycogen and,
• Gluconeogenesis from lactate, amino acids, and glycerol
in the liver, kidneys and intestines

17. PHASE III
(PROLONGED STARVATION)
• Limits the need for gluconeogenesis and thereby conserve
body protein .
• Increase utilization of lipid-derived fuels
• The second is a change in the fuels used by the brain.
• During early starvation, the CNS continues to use glucose as its
exclusive fuel.
• as starvation is prolonged it uses ketone bodies
• Decrease in plasma leptin, which by diminishing sympathetic
nervous system activity, would diminish the basal metabolic
rate.

19. PHASE IV
• Gluconeogenesis still decreases and more ketone body
formed.
• Brain starts using both glucose and more of ketone
body.
• RBCs, renal medulla still utilize glucose.

21. PHASE V
(VERY PROLONGED
STARVATION )
• Occurs in very prolonged starvation and extreme obese
individuals.
• Very less glucose utilized
• Almost all tissues use ketone bodies or fatty acids.

22. FACTORS REGULATING
• Hormonal factors
• Insulin
• Glucagon
• Cortisol
• Epinephrine
• Growth hormone
• Thyroid hormone
• Somatostatin
• Pancreatic polypeptide.

23. NON-HORMONAL REGULATION
• Changes in the concentrations of the fuels themselves may also
play a direct role.
• Increase in circulating glucose levels
• Diminish hepatic gluconeogenesis & glycogenolysis
• Enhance glycogen synthesis
• FFAs stimulate hepatic gluconeogenesis;
• Recent studies suggest
• anti-gluconeogenic action of insulin may be secondary to its
antilipolytic action on the fat cell

24. HORMONES
• Insulin
• Hypoglycemic hormone
• Favors glycogenesis
• Promotes glycolysis
• Inhibits gluconeogenesis
• Anabolic hormone
• Helps in storage of glycogen, lipids & protein

25. ACTIONS OF INSULIN
• Rapid (seconds)
• Increased transport of glucose, amino acids
• K+ into insulin-sensitive cells
• Intermediate (minutes)
• Stimulation of protein synthesis
• Inhibition of protein degradation
• Activation of glycolytic enzymes and glycogen synthase
• Inhibition of phosphorylase and gluconeogenic enzymes
• Delayed (hours)
• Increase in mRNAs for lipogenic and other enzymes

26. ADIPOSE TISSUE
• Increased glucose entry
• Increased fatty acid
synthesis
• Increased glycerol phosphate
synthesis
• Increased triglyceride
deposition
• Activation of lipoprotein
lipase
• Inhibition of hormone-
sensitive lipase
• Increased K+ uptake
MUSCLE
• Increased glucose entry
• Increased glycogen
synthesis
• Increased amino acid
uptake
• Increased protein synthesis
by ribosomes
• Decreased protein
catabolism
• Decreased release of
gluconeogenic amino acids
• Increased ketone uptake
• Increased K+ uptake

27. • Liver
• Decreased ketogenesis
• Increased protein synthesis
• Increased lipid synthesis
• Decreased glucose output due to decreased
gluconeogenesis,
• Increased glycogen synthesis, and
• Increased glycolysis
• General
• Increased cell growth

28. GLUCAGON
• Hyperglycemic hormone
• Promotes glycogenolysis
• Enhances gluconeogenesis
• Depresses glycogen synthesis
• Inhibits glycolysis
• It acts via Gs to activate adenylyl cyclase and increase
intracellular cAMP.
• This leads via protein kinase A to activation of phosphorylase
and therefore to increased breakdown of glycogen and an
increase in plasma glucose

29. EFFECTS OF GLUCAGON ON
ENZYMES• Phosphoenolpyruvate carboxykinase, which facilitates
the conversion of oxaloacetate to phosphoenolpyruvate.
• Fructose 1,6-diphosphatase, which catalyzes the
conversion of fructose diphosphate to fructose 6-
phosphate.
• Glucose 6-phosphatase, which controls the entry of
glucose into the circulation from the liver.

30. INSULIN:GLUCAGON
MOLAR RATIO
• Insulin –glucagon molar ratio on a balanced diet is
approximately 2.3
• When energy is needed during starvation, the insulin–
glucagon molar ratio is low, favouring glycogen breakdown
and gluconeogenesis.
• When the need for energy mobilization is low, the ratio is
high, favouring the deposition of glycogen, protein, and fat.

31. CORTISOL
• The glucocorticoids are necessary for glucagon to exert its
gluconeogenic action during fasting.
• They are gluconeogenic themselves
Carbohydrate/lipid metabolism:
• Hepatic glycogen deposition
• Peripheral insulin resistance
• Gluconeogenesis
• Free fatty acid production
• Overall diabetogenic effect

32. CORTISOL EFFECTS…
• Metabolic PPAR-γ
• Tryptophan hydroxylase
• Tyrosine aminotransferase
• Metalloprotease
• Glutamine synthase
• Glycogen synthase
• Glucose-6-phosphatase
• PEPCK
• γ-Fibrinogen
• Cholesterol 7α-hydroxylase

33. CATECHOLAMINES
• Catecholamines have a dual effect on insulin secretion;
• They inhibit insulin secretion via α2-adrenergic receptors and
• Stimulate insulin secretion via β2-adrenergic receptors.
• The net effect of epinephrine and norepinephrine is usually
inhibition.
• Major role in muscle glycogenolysis by increasing cAMP
levels.

34. GROWTH HORMONE
• The effects of growth hormone are partly direct and partly
mediated via IGF-I.
• Growth hormone mobilizes FFA from adipose tissue, thus
favoring ketogenesis.
• It decreases glucose uptake into some tissues ("anti-insulin
action"), increases hepatic glucose output & decrease tissue
binding of insulin

35. SOMATOSTATIN
• Somatostatin 14 (SS 14) and its amino terminal-extended
form somatostatin 28 (SS 28) are found in the D cells of
pancreatic islets.
• Both forms inhibit the secretion of insulin, glucagon, and
pancreatic polypeptide and act locally within the pancreatic
islets in a paracrine fashion.
• SS 28 is more active than SS 14 in inhibiting insulin
secretion, and it apparently acts via the SSTR5 receptor

36. PANCREATIC POLYPEPTIDE
• Its secretion is increased by a meal containing protein and by
fasting, exercise, and acute hypoglycemia

37. THYROID HORMONES
• Thyroid hormones make experimental diabetes worse.
• The principal diabetogenic effect of thyroid hormones is to
increase absorption of glucose from the intestine,
• But the hormones also cause (probably by potentiating the
effects of catecholamines) some degree of hepatic glycogen
depletion.

38. BGR IN SPECIAL
SITUATIONS…• Stress and injury
• Pregnancy & lactation
• Exercise
• Obesity
• Cancer
• Liver and renal disorder

39. STRESS AND INJURYDefinition
• Any injury
• Surgery
• Renal failure
• Burns
• Infection

40. • Increase need of glucose for increased demand.
• Increase in hyperglycemic hormones.
• Blood cortisol
• Glucagon
• Catecholamines
• Growth hormone.
• Resistance to insulin
• Catabolic and less anabolic
• BMR, blood glucose and FFA increased.
• For unknown reasons ketogenesis in not increased

41. Mechanism
• Cytokines released in response to injury and infection.
• IL-1 – activates proteolysis
• IL-6- responsible for fever
• TNF α
• Suppress adipocyte TAG synthesis
• Inhibits lipoprotein lipase
• Stimulates lipolysis
• Inhibits insulin release and promotes insulin resistance.

42. PREGNANCY
• Fetus needs energy
• Mainly uses glucose, FFA, lactate & KB.
• Placental lactogen (PL) , estrogen and progestrone important
hormones.
• PL- lipolysis
• Steroid hormones- insulin resistance
• Post prandial duration reduced in mother.
• In fed state- glucose, insulin are increased.

43. • Maternal hypoglycemia can be reached too early as fetus
needs for its growth.
• Frequent small meals advised
• If other factors present like obesity then maternal
hyperglycemia will lead to GDM.
• Due to Insulin resistance.
• Swings in hormones & fuels are exaggerated in pregnancy.
• Lactation
• Breast use glucose for milk production
• Hormonal effect

44. EXERCISE
• Aerobic and anaerobic exercise
• Insulin mediated glucose absorption by GLUT 4 mechanism
• Vessels constricted due to muscle contraction
• Depend on glycogen
INSTANT ENERGY
• Phosphocreatine
• FFA used in aerobic exercise…

45. LIVER DISEASES
• Mainly affects AA.
• Fails to produce glucose
• Affects production of IGFs
• Hypoglycemia can cause
death.
• Wasting seen due to
impaired action of IGF and
GH
RENAL DISEASES
• Mainly affects protein and
AA.
• Loss of carnitine especially
in dialysis
• Affects fatty acid metabolism
which in turn affect blood
glucose levels.

46. OBESITY
• Important cause of insulin resistance
• Reduces receptor number.
• Decreases affinity
• Affects GLUT transport towards cell membrane.
• Severity of obesity to insulin resistance.
• Mechanism
• Adipokines and adiponectin reduced
• Resistin, TNF increased

47. CANCER
• Cells function independently of starve feed cycle.
• Use more glucose and Aas
• Warburg hypothesis
• Cancer cachexia
• Hypoxia-inducible factors (HIFs) responsible.
• Anaerobic state.
• Activate GLUT transporter.
• Activate glycolysis enzymes especially PDH

48. SUMMARY…
• Glucose essential for vital organs…
• Brain needs constant supply of energy..
• Tightly regulated for its constant supply..