Modeling and Control of Biological Systems

3. Fundamentals on Glucose
Metabolism

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 GLUCOSE MOLECULE

H
CH2OH O
HO
H
H
HO OH
HO
H H

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 GLUCOSE TURNOVER

PRODUCTION GLUCOSE UTILIZATION

POOL
(25-32 g)

Turnover in 24 hours: ~280 g

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 DAYLY GLYCEMIC PATTERN

CONCENTRATION

BREAKFAST LUNCH DINNER

TIME (hour)

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GLUCOSE PRODUCTION

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Where does BLOOD GLUCOSE come from?

GLUCOSE-6-
PHOSPHATE
Dephosphorylation Glucose-6-phosphatase

BLOOD INTESTINAL
GLUCOSE ABSORPTION

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 Where does GLUCOSE-6-P come from?

GLYCOGENOLYSIS GLUCOSE-6- GLUCONEOGENESIS

PHOSPHATE
Dephosphorylation Glucose-6-phosphatase

BLOOD INTESTINAL
GLUCOSE ABSORPTION

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GLUCOSE UTILIZATION

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 Where does BLOOD GLUCOSE go?
GLYCOGENOLYSIS GLUCOSE-6- GLUCONEOGENESIS
PHOSPHATE
Dephosphorylation Glucose-6-phosphatase

BLOOD INTESTINAL
GLUCOSE ABSORPTION

Transmembrane
Transporter
Transport

INTRACELLULAR
GLUCOSE
Phosphorylation Hexokinase

GLYCOGEN- GLUCOSE-6- GLYCOLYSIS

SYNTHESIS PHOSPHATE OXIDATION

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 ORGANS PRODUCING GLUCOSE

1. LIVER
• quantitatively major contributor (at least
>80 %) from both glycogenolysis and
gluconeogenesis

2. KIDNEYS
• quantitatively minor role, excluding
prolonged fasting periods (> 4-5 days),
almost exclusively from gluconeogenesis

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 ORGANS UTILIZING GLUCOSE

1. GLUCOSE-DEPENDENT ORGANS
• Brain, red blood cells
• Constant glucose utilization (~100 mg/min, ~150 g/day)
• Absolute need of glucose: survival in danger!
• Risk: hypoglycemia

2. INSULIN-DEPENDENT ORGANS
• Muscle tissue, heart, adipose tissue
• Phasic glucose utilization
• Glucose utilization dependent on insulin
• Insulin is a hormone secreted by the pancreatic β-cells at each
meal

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 DAYLY INSULINEMIC PATTERN

CONCENTRATION

BREAKFAST LUNCH DINNER

TIME (hour)

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 HORMONES

• Chemical messengers which coordinate different cellular

activities in multicellular organisms
• Molecules of different chemical nature (mostly from
proteins)
• Molecules synthesized by tissues or specific organs
(endocrine glands)
• Secreted directly into the blood which transports them
to their sites of action
• Change in specific manner the activity of tissues that are
sensitive to them (target organs or cells)

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 A SCHEME of GLUCOSE-INSULIN CONTROL SYSTEM

GLYCOGENOLYSIS GLUCOSE-6- GLUCONEOGENESIS

PHOSPHATE
Dephosphorylation Glucose-6-phosphatase

BLOOD INTESTINAL
GLUCOSE ABSORPTION
INSULIN
Transmembrane
Transporter
Transport

INTRACELLULAR
GLUCOSE
Phosphorylation Hexokinase

GLYCOGEN- GLUCOSE-6- GLYCOLYSIS

SYNTHESIS PHOSPHATE OXIDATION
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GLUCOSE TRANSPORT

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 GLUCOSE-SENSING ORGANS

1. Pancreatic β-cell
• senses glycemia and secretes insulin

2. Liver
• senses glycemia and modulates glucose production

3. Ventromedial hypothalamus
• senses glycemia and, if it is lower than a threshold value (65-70
mg/dl), coordinates the counterregulatory response of insulin
antagonist hormones, e.g. glucagon, epinephrine, cortisol etc,
which have, a hyperglycemic effect.

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 A HIGH LEVEL SCHEME of GLUCOSE-INSULIN
CONTROL SYSTEM
GLUCOSE-SENSING
PANCREATIC β-CELL
(negative feedback)

INSULIN-DEPENDENT
INSULIN ORGANS
(Muscle, Adipose Tissue)
GLUCOSE-PRODUCING
ORGANS
BLOOD
(Liver, Kidneys) GLUCOSE
GLUCOSE-DEPENDENT
GLUCOSE-SENSING ORGANS
LIVER (CNS, Red Blood Cells)
(negative feedback)
GLUCOSE-SENSING
HYPOTHALAMUS
(threshold)

INTESTINAL
ABSORPTION
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 DIABETES DIAGNOSIS

1. GLYCEMIA ≥ 140 mg/dl fasting glucose level

• steady state
• glucose control dominated by “glucosesensor”
organs
or

2. GLYCEMIA ≥ 200 mg/dl 120’ after an oral glucose load

• non-steady state
• glucose control with important role of “insulin-
dependent” organs

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References:

CB_Chapter01.pdf – downloadable from the course web page

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