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Blood glucose homeostasis
1. Blood glucose Homeostasis
ďźHormonal regulation of blood glucose
ďźGlucose homeostasis in fed and fasting state
ďźFed-fast cycles
ďźHypo and hyperglycemia
ďźDifference Between Type I and Type II DM
2. Definition of Glucose Homeostasis
⢠The process of maintaining blood glucose at a
steady-state level is called âglucose
homeostasisâ [DeFronzo, 1988].
⢠This is accomplished by the finely hormone
regulation of peripheral glucose uptake,
hepatic glucose production, and glucose
uptake during carbohydrates ingestion.
3. Importance of blood Glucose
Homeostasis
⢠Glucose is an obligate metabolic fuel for many tissues(RBC)
and organs(Brain and Kidney).
⢠Severe hypoglycemia can cause seizures, loss of
consciousness, and death
⢠Chronic hyperglycemia leads to ;
ďź Diabetes mellitus
ďź Gylcation of protein that results in neuropathy, retinopathy
and nephropathy
ďź Various other complications
Therefore, blood glucose concentrations need to be maintained
within narrow limits.
5. NORMALBLOOD
GLUCOSE
REGULATION OF BLOOD GLUCOSE
The plasma
glucose level
depends on the
balance
between
glucose
entering and
leaving the
extracellular
fluid
GLYCOGENESISGLYCOLYSIS
GLUCONEOGENESISGLYCOGENOLYSIS
LIPOGENESIS
DIET
Use Storage Conversion
Supply
6. FACTORS MAINTAINING BLOOD
GLUCOSE
Factors which cause entry
of
glucose into blood
⢠Absorption from
intestines
⢠Glycogenolysis
⢠Gluconeogenesis
⢠Hyperglycemic
hormones
Factors leading to
depletion of glucose in
blood
⢠Utilization by tissues for
energy
⢠Glycogen synthesis
⢠Conversion of glucose
into fat
⢠Hypoglycemic hormone
8. HORMONAL REGULATION
The pancreas
detects the
change in
blood glucose
concentration
and releases
the
appropriate
hormone
High
blood
glucose
Signal
to
release
Hypoglycemic
hormone
insulin
Low
blood
glucose
Hyperglycemic
hormone
glucagon
14. Phases of glucose homeostasis
6/17/2017 Biochemistry for medics- Lecture notes 14
Phase 1 Phase 2 Phase 3 Phase 4
Nutritional
status
Well fed
state
Post- Absorptive
state
Fasting Prolonged
fasting/
Starvation
Source of
glucose
Diet Hepatic glycogen
and
Gluconeogenesis
Hepatic and
Renal
gluconeogenesis
Renal and
hepatic
gluconeogenesis
Tissues
using
glucose
All All tissues, but in
Liver, muscle and
adipose tissue, the
rate of utilization is
slowed.
Brain and RBCs
and cells lacking
mitochondria;
small amount by
muscle.
Brain at a slower
rate, RBCs
normal rate
Major fuel
of brain
Glucose Glucose Glucose and
ketone bodies
Ketone bodies
and glucose
19. Carbohydrate metabolism in liver during fed state
Insulin /glucagon:
Carbohydtate metabolism
⢠activity of glucokinase Glucose -6-phosphate
⢠Activation of glycogen synthase Glycogenesis
⢠activity of HMP shunt for production of NADPH which is used
for lipogenesis
⢠activity of pyruvate kianse and PDH glycolysis
⢠gluconeogenesis
Lipid metabolism
citrate and NADPH activates acetyl Co A carboxylase fatty
acid synthesis
TAG synthesis
20. amino acid metabolism
⢠amino acids used by liver and other organs for
protein synthesis.
⢠Excess amino acids catabolized by liver to yield
urea. Carbons used mainly for fatty acid
synthesis
22. Metabolism in adipose tissue in fed stateCarbohydrtaemetabolism
1.Influx of glucose in cell
via GLUT -4 transporter
2. Increased glycolysis
3.Increased activity of
HMP shunt
Lipidmetabolism
1.Increased fatty acid
synthesis
2, increased TAG synthesis
24. Metabolism in resting muscle during
fed state
Carbohydrate
metabolism
⢠increase in
glucose transport
into muscle cells
by GLUT-4
⢠increased
glycogenesis
⢠Increased
glycolysis
Lipid
metabolism
⢠fatty acids are
of secondary
importance as
a fuel for
muscle during
the fed state
Amino acid
metabolism
⢠increased protein
syntheis
⢠Increased uptake
of branched chain
amino acid
26. Metabolism in brain during fed state
⢠Carbohydrate metabolism
In the fed state, the brain uses glucose
exclusively as a fuel, completely oxidizing
approximately 140 g/day to CO2 and H2O.
⢠Fat metabolism
fatty acids circulating in the blood make little
contribution to energy production
29. Metabolism in liver during starvation
Carbohydrate metabolism
Increased glucagon/insulin ratio
⢠Increased glycogenolysis ; it is early response to
fasting and provides blood glucose over a period
of 10-18 hours
⢠Increased gluconeogenesis; glucagon activates
PEPCK
Lipid metabolism
⢠Increased fatty acid oxidation
⢠Increased ketogenesis during prolonged
starvation
30. ⢠amino acid metabolism
amino acids are utilized for guconeogenesis
32. Metabolism in adipose tissue during
starvation
Increased glucagon/insulin ration
⢠Carbohydrate metabolism
decreased utilization of glucose by depress activity
of GLUT -4
⢠Lipid metabolism
Increased degradation of TAG due to activation of
hormone sensitive lipase by glucagon
Increased release and oxidation of fatty acid
Glycerol part of fat is substrate for gluconeogenesis
34. Metabolism in resting muscle during
starvation
⢠Resting muscle uses fatty acids as its major fuel source.
By contrast, exercising muscle initially uses its glycogen
stores as a source of energy. G-6-p from
glycogenolysis is converted to lactic acid in
exercising muscle
⢠Carbohydrate metabolism
Low insulin glucagon ration leads to decreased
transport of glucose by GLUT -4
35. ⢠Lipid metabolism
During the first 2 weeks of fasting, muscle uses fatty acids
from adipose tissue and ketone bodies from the liver as
fuels
After about 3 weeks of fasting, muscle decreases its use
of ketone bodies and oxidizes fatty acids almost
exclusively.
⢠Amino acid metabolism
In early days of fasting muscle protein breaks down rapidly
for gluconeogenesis
Glutamate and alanine are predominent glucogenic amino
acid
After several days of fasting rate of proteolysis decreases
because now more ketone bodies are utilized by brain
compared to glucose from gluconeogenesis
37. Metabolism in brain during starvation
⢠carbohydrate metabolism
During the first days of fasting, the brain
continues to use glucose exclusively as a fuel
provided by hepatic gluconeogenesis.
⢠Ketolysis
In prolonged fasting(greater than 2â3 weeks),
plasma ketone bodies reach significantly
elevated levels, and replace glucose as the
primary fuel for the brain
38. Metabolism in kidney during
starvation
⢠during starvation about 50% of
gluconeogenesis occurs here.
39. G-6-P
Pyruvate
Acetyl CoA TCA
Glycogen
HMP
shunt
Glucose
Fatty acid
TAG
Amio acid
protein
VLDL
Glucose
GLUT-4
Glucose
G-6-P
Pyruvate
ACetyl CoA
TCA
Fatty acid
VLDL TAG
Chylomicrons
GlucoseGLUT-4
G-6-P
Glycogen
Glycolysis
Amino acid
Protein
G-6-P
Glycolysis
HMP
shunt
Insulin/glucagon
Intertissue relationships in the absorptive state.
GLUT-2
GLUT-3
Liver
Muscle
Brain
Adipose
tissue
40. Glycogen
G-6-P Glucose
TCA
Glucose
Acetyl CoA
Ketone bodies
TCA
TAG
Fatty acid
Glycerol
Fatty acid
Ketone bobies
Ketone bodies
Ketone bodiesAcetyl CoATCA
protein
Amino acid
Acetyl CoA
TCA
Liver
Adipose tissue
Muscle
Brain
Intertissue relationships during starvation
Glucagon
Epinephrine
Cortisol
42. Hypoglycemia
⢠Hypoglycemia- Decrease in blood glucose
below the normal is called hypoglycemia.
⢠Hypoglycemia is a laboratory âdiagnosisâ which
is usually considered a blood glucose level
below 60 mg/dL.
⢠Symptoms begin at plasma glucose levels in
the range of 60 mg/dL and
⢠Impairment of brain function at
approximately 50 mg/dL.
43. Common causes of hypoglycemia
6/17/2017 Biochemistry for medics- Lecture notes 43
o Endogenous hyperinsulinism
o Insulinoma
o Ectopic insulin secretion
o Congenital hyperinsulinism and
o Enzyme deficiencies- Glycogen storage disease
o Hormonal deficiencies:Cortisol, growth
hormone, or both, Glucagon and epinephrine
44. Hyperglycemia
Increase in blood glucose level above the normal
physiological limit is called as Hyperglycemia
Causes of hyperglycemia
o Diabetes mellitus
o Diseases of pancreas(pancreatitis, hemochromatosis,
carcinoma head of pancreas,)
o Acromegaly,
o Cushing's syndrome,
o Glucagonoma and
o Pheochromocytoma
o Hyperthyroidism
45. Definition of Diabetes Mellitus
⢠Diabetes is a group of metabolic diseases
characterized by hyperglycemia resulting from
defects in insulin secretion, insulin action, or
both.
46. Classification of Diabetes mellitus
⢠Diabetes can be classified into the following general
categories:
⢠1. Type 1 diabetes (due to ᾌ-cell destruction, usually
leading to absolute insulin deficiency)
⢠2. Type 2 diabetes (due to a progressive insulin secretory
defect on the background of insulin resistance)
⢠3. Other specific diabetes
Gestational diabetes mellitus (GDM) (diabetes diagnosed
in the second or third trimester of pregnancy that is not
clearly overt diabetes)
IGT(Impaired Glucose tolerance)
IFG(Impaired Fasting Glucose)