Download Blood glucose homeostasis

CLINICAL CHEMISTRY (MLT 301)
CARBOHYDRATE
LECTURE ONE
Dr. Essam H. Jiffri
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Introduction
Carbohydrates are distributed widely in the body,
and have:
- Metabolic functions
- Glucose (the principal form and the major fuel for
cellular metabolism)
- Structural functions:
- the precursor of other sugars, such as ribose
which is found in:
• nucleic acids, and of the
• carbohydrate moieties of glycoproteins
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Introduction
Man can synthesize some carbohydrate
from substrates such as:
- Glycerol and,
- Amino acids but most is derived from plant
sources
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Blood glucose homeostasis
Sources:
Blood glucose is maintained from several sources
including:
- Diet
- Ingested carbohydrate includes both:
- Digestible form (starch or disaccharides-after digestion
are absorbed as glucose, galactose or fructose)
- Nondigestible forms (dietary fibre)
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Blood glucose homeostasis
-THE LIVER
The liver is an important organ in blood glucose homeostasis
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Blood glucose homeostasis
-THE LIVER
• After feeding (stores some excess glucose as
glycogen)
• In the fasted state (through glycogenolysis and
gluconeogenesis, maintains blood levels)
• The hepatic uptake and output of glucose is
controlled by:
o the concentration of key intermediates, and
o The activity of enzymes.
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Blood glucose homeostasis
-THE LIVER
• In hepatocytes, glucose phosphorylation is
promoted by glucokinase which has a lower
affinity than hexokinase.
• The activity of glucokinase increases with high
blood glucose levels and the liver removes
glucose from the portal blood after a meal.
• After uptake and phosphorylation, excess
glucose is stored in the liver as glycogen.
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Blood glucose homeostasis
Glycogenolysis
- The process by which
glucose is released
from the liver
(phosphorylase the key
regulatory enzyme )
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Blood glucose homeostasis
Glycogenolysis
-In well-fed individuals hepatic glycogen
stores can account for up to 10% of organ
weight.
-It forms a buffer which maintains blood
glucose levels between meals.
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Blood glucose homeostasis
Gluconeogenesis
- Other compounds are also converted to glucose in the
liver
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Blood glucose homeostasis
Gluconeogenesis
- lactate, glycerol and amino acids,
particularly alanine, are gluconeogenic
substrates.
- Lactate is continually produced by partial
oxidation of glucose in muscle and
erythrocytes and is reconverted to
glucose in the liver by the (Cori cycle )
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Cori cycle
Liver
Blood
Glucose
Glucose-6-phosphate
Lactate
Lactate
CO2 + H2O
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Muscle (glycogen(
Blood glucose homeostasis
Hormonal regulation
-carbohydrate-rich meal also affects the release of
several hormones:
-Insulin is the major hypoglycaemic hormone
-Other hormones, including glucagon, growth
hormone, cortisol and adrenaline are counterregulatory; these antagonize the effects of: insulin
and have gluconeogenic effects.
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Blood glucose homeostasis
Insulin
-Insulin is synthesized
by the B (or β) cells in
the islets of Langerhans
of the pancreas.
-Glucose stimulates
insulin release
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Blood glucose homeostasis
Insulin
-Insulin is an anabolic hormone which
stimulates:
- glucose uptake by muscle and adipose
tissue, and increases:
• protein synthesis,
• glycogen synthesis
• lipogenesis.
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Blood glucose homeostasis
Glucagon
-Glucagon is synthesized in the A (or α) cells
of the pancreas.
-Inhibited by glucose and insulin
-Glucagon stimulates:
• glycogenolysis and
• gluconeogenesis (raising blood glucose
concentrations).
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Blood glucose homeostasis
Growth Hormone
-Growth hormone secretion is stimulated by
hypoglycaemia
-Actions include:
• increased hepatic glucose production, and
• increased lipolysis and raising plasma
NEFA levels.
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Blood glucose homeostasis
Adrenaline
-Hypoglycaemia is a potent stimulus for
adrenaline secretion.
• Inhibits insulin secretion
• stimulates adipose tissue lipolysis,
• increasing NEF A production
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Blood glucose homeostasis
Cortisol
-Cortisol stimulates:
• hepatic gluconeogenesis
• promotes adipose tissue lipolysis and
NEFA release
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INTERRELATION OF GLUCOSE,
NONESTERIFIED FATTY ACID AND KETONE
BODY METABOLISM
-Muscle has a higher rate of fuel utilization
than other organs during exercise.
-The brain, kidney and intestine utilize a
higher percentage of available glucose at
rest.
-Alternative fuels are required during
prolonged fasting or starvation
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INTERRELATION OF GLUCOSE,
NONESTERIFIED FATTY ACID AND KETONE
BODY METABOLISM
-The ketone bodies derived from fatty acid
metabolism in the liver :
• acetone
• acetoacetate, and
• β-hydroxybutyrate,
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INTERRELATION OF GLUCOSE,
NONESTERIFIED FATTY ACID AND KETONE
BODY METABOLISM
•
•
NEFA from adipose tissue is controlled by:
the activity of hormon-sensitive lipase.
Insulin inhibits this enzyme (anti-lipolytic)
adrenaline, growth hormone, glucagon
and cortisol are lipolytic.
- Greater fluxes of NEFAs occur if
carbohydrate availability is limited.
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INTERRELATION OF GLUCOSE,
NONESTERIFIED FATTY ACID AND KETONE
BODY METABOLISM
-NEFAs are transported in blood bound to
albumin; about 30% is extracted by the
liver.
-In the liver, NEFAs are either:
• reesterified to form triglycerides or,
• metabolized by Beta-oxidation in
mitochondria to form acetyl CoA
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KEY POINTS
Ketone bodies are produced from NEFA in the liver
Ketone bodies are a alternative fuel
for brain metabolism
In the starvation many organs utilize
ketones, sparing glucose
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