Chapter 22b
Metabolism and
Energy Balance
Homeostatic Control of Metabolism
• Endocrine pancreas secretes hormones
insulin and glucagon. These control blood
sugar.
Figure 22-8a
Homeostatic Control of Metabolism
Figure 22-8b
Homeostatic Control of Metabolism
• In the fed state, high levels of plasma glucose and amino
acids result in the secretion of insulin.
•
Note effects of insulin √
Figure 22-9a
Homeostatic Control of Metabolism
• In the fasting state, low plasma glucose
results in the secretion of glucagon
• Note effects of glucagon √
Figure 22-9b
Homeostatic Control of Metabolism
• Levels of glucose, glucagon, and insulin vary
over a typical 24-hour period
Figure 22-10
Factors That Control Insulin Secretion
1 - Increased plasma glucose
2 - Increased plasma amino acids
3 - Feedforward effects of GI hormones
4 - Parasympathetic activity
5 - Sympathetic activity
Insulin Promotes Anabolism
• Increases glucose transport into most, but not
all, insulin-sensitive cells
• Enhances cellular utilization and storage of
glucose
• Enhances utilization of amino acids
• Promotes fat synthesis
Glucose Uptake by Adipose Tissue and Resting
Skeletal Muscle is Insulin-Sensitive
• In the
absence of
insulin,
glucose
cannot enter
cell
Figure 22-12a
Insulin Enables Glucose Uptake by Adipose Tissue
and Resting Skeletal Muscle
• Insulin
signals the
cell
Figure 22-12b
Insulin Indirectly Alters Glucose Transport in
Hepatocytes
• Hepatocyte in
fed state
Figure 22-13a
Insulin Indirectly Alters Glucose Transport in
Hepatocytes
• Hepatocyte
in fasted
state
Figure 22-13b
Fed State: Insulin is an Anabolic Hormone
• Insulin promotes
• Glucose uptake
• Glucose
metabolism
• Energy storage
as glycogen and
fat
KEY
Plasma
glucose
Stimulus
Integrating center
Efferent path
 cells
of pancreas
 cells
of pancreas
Effector
Tissue response
Systemic response
Insulin
Liver
Muscle, adipose,
and other cells
Glucose transport
Glycolysis
Glycogenesis
Lipogenesis
Negative
feedback
Plasma
glucose
Figure 22-14
Glucagon Is Dominant in the Fasted State
• Glucagon is anatgonistic to most actions of
insulin, resulting in a catabolic state in the
body
Figure 22-9b
Endocrine Response to Hypoglycemia
Figure 22-15
Diabetes Mellitus is a Family of Diseases
• Diabetes mellitus is a condition characterized
by chronic elevated plasma glucose levels, or
hyperglycemia
• Diabetes is reaching epidemic proportions in
the USA
• Complications of diabetes affect many body
systems
• The two types of diabetes are
•
•
Type 1 - characterized by insulin deficiency
Type 2 - known as insulin-resistant diabetes
(cells cannot respond to the insulin in the
body)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
• Overview
• See pages
743 - 745
Plasma
fatty acids
Plasma
amino acids
Plasma
glucose
No insulin released
Fat
breakdown
Glucose uptake
(muscle and adipose)
Fat
storage
Liver
Plasma
fatty acids
Ketone
production
Substrate for
ATP production
Tissue
loss
Glucose utilization
Glycogenolysis
Gluconeogenesis
Hyperglycemia
METABOLIC
ACIDOSIS
Brain interprets
as starvation
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Polyphagia
Tissue
loss
DEHYDRATION
Exceeds renal
threshold for glucose
Glucosuria
Ventilation
Osmotic diuresis
and polyuria
Metabolic
acidosis
Urine
acidification
and
hyperkalemia
Thirst
Dehydration
Lactic acid
production
Anaerobic
metabolism
Blood volume
and
Blood pressure
Circulatory
failure
Polydipsia
ADH secretion
Attempted compensation
by cardiovascular
control center
compensation
fails
Coma or
death
Figure 22-16
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
1 - Absorption
of nutrients is
normal
Plasma
fatty acids
Plasma
glucose
Plasma
amino acids
Figure 22-16 (1 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
2a (protein) Most cells
unable to
absorb
nutrients shift to
fasted state
metabolism
Plasma
fatty acids
Plasma
glucose
Plasma
amino acids
No insulin released
Amino acid
uptake by
most cells
Liver
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Tissue
loss
Figure 22-16 (2 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
2b (fat) - Most
cells unable to
absorb
nutrients shift to
fasted state
metabolism
Plasma
fatty acids
Plasma
glucose
Plasma
amino acids
No insulin released
Fat
breakdown
Plasma
fatty acids
Substrate for
ATP production
Tissue
loss
Amino acid
uptake by
most cells
Fat
storage
Liver
Ketone
production
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Tissue
loss
Figure 22-16 (3 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
3Hyperglycemia
results when
liver cells also
shift to the
fasted state, and
produce more
glucose!
Plasma
fatty acids
Plasma
glucose
Plasma
amino acids
No insulin released
Fat
breakdown
Fat
storage
Plasma
fatty acids
Substrate for
ATP production
Tissue
loss
Glucose uptake
(muscle and adipose)
Glucose utilization
Liver
Ketone
production
Glycogenolysis
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Gluconeogenesis
Hyperglycemia
Substrate
for ATP
production
Tissue
loss
Figure 22-16 (4 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
3b – More
glucose results
in polyphagia
Plasma
fatty acids
Plasma
amino acids
Plasma
glucose
No insulin released
Fat
breakdown
Fat
storage
Plasma
fatty acids
Substrate for
ATP production
Tissue
loss
Glucose uptake
(muscle and adipose)
Glucose utilization
Liver
Ketone
production
Glycogenolysis
Gluconeogenesis
Hyperglycemia
Brain interprets
as starvation
Polyphagia
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Tissue
loss
Figure 22-16 (5 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
4a Hyperglycemia
results in
glucose in the
urine and
increased urine
production
Plasma
fatty acids
Plasma
amino acids
Plasma
glucose
No insulin released
Fat
breakdown
Fat
storage
Plasma
fatty acids
Substrate for
ATP production
Glucose uptake
(muscle and adipose)
Glucose utilization
Liver
Ketone
production
Glycogenolysis
Gluconeogenesis
Hyperglycemia
Tissue
loss
Brain interprets
as starvation
Polyphagia
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Tissue
loss
Exceeds renal
threshold for glucose
Glucosuria
Osmotic diuresis
and polyuria
Figure 22-16 (6 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
4b – And then
low blood
pressure as a
result of
dehydration
Plasma
fatty acids
Plasma
amino acids
Plasma
glucose
No insulin released
Fat
breakdown
Fat
storage
Plasma
fatty acids
Substrate for
ATP production
Glucose uptake
(muscle and adipose)
Glucose utilization
Liver
Ketone
production
Glycogenolysis
Gluconeogenesis
Hyperglycemia
Tissue
loss
Brain interprets
as starvation
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Polyphagia
Tissue
loss
DEHYDRATION
Exceeds renal
threshold for glucose
Glucosuria
Osmotic diuresis
and polyuria
Thirst
Dehydration
Blood volume
and
Blood pressure
Polydipsia
ADH secretion
Attempted compensation
by cardiovascular
control center
Figure 22-16 (7 of 8)
Acute Pathophysiology of Type 1 Diabetes Mellitus
ACUTE PATHOPHYSIOLOGY OF TYPE 1 DIABETES MELLITUS
FAT METABOLISM
GLUCOSE METABOLISM
PROTEIN METABOLISM
Meal
absorbed
5 - Metabolic
acidosis results,
which if
untreated can
lead to coma
and/or death
Plasma
fatty acids
Plasma
amino acids
Plasma
glucose
No insulin released
Fat
breakdown
Glucose uptake
(muscle and adipose)
Fat
storage
Liver
Plasma
fatty acids
Ketone
production
Substrate for
ATP production
Tissue
loss
Glucose utilization
Glycogenolysis
Gluconeogenesis
Hyperglycemia
METABOLIC
ACIDOSIS
Brain interprets
as starvation
Amino acid
uptake by
most cells
Protein
breakdown,
especially muscle
Plasma
amino acids
Substrate
for ATP
production
Polyphagia
Tissue
loss
DEHYDRATION
Exceeds renal
threshold for glucose
Glucosuria
Ventilation
Osmotic diuresis
and polyuria
Metabolic
acidosis
Urine
acidification
and
hyperkalemia
Thirst
Dehydration
Lactic acid
production
Anaerobic
metabolism
Blood volume
and
Blood pressure
Circulatory
failure
Polydipsia
ADH secretion
Attempted compensation
by cardiovascular
control center
compensation
fails
Coma or
death
Figure 22-16 (8 of 8)
Type 2 Diabetes
• Accounts for 90% of all diabetics
• Insulin resistance (target cells do not respond
normally)
• Early symptoms are mild, but later
complications include atherosclerosis,
neurological changes, renal failure, and
blindness
• Therapy
• Diet and physical exercise
• Drugs
Glucose Tolerance Test
Figure 22-17
Drugs Attempt to Treat Diabetes by Varying
Mechanisms
Table 22-6
Metabolic Syndrome - Insulin resistance syndrome
• Patients have combined symptoms of type 2
diabetes, atherosclerosis, and high blood
pressure
• Diagnostic criteria - three or more of
•
•
•
•
•
Central (visceral) obesity
Blood pressure ≥ 130/85 mm Hg
Fasting blood glucose ≥ 110 mg/dL
Elevated fasting plasma triglyceride levels
Low plasma HDL-C levels
Fats
• Assembled into chylomicrons in SI lining
• Into lymphatics to blood to liver
• Liver processes into lipoproteins LDL’s
• LDL’s to cells for use in synthesis of cholesterol
• Likely leads to atherosclerosis
• HDL’s depleted of cholesterol tend to return to
liver for processing into bile for excretion –
lowers cholesterol
• HMG coA reductase inhibitors – Big $$
• statins – lipitor lovastatin also other cholesterol
treatments: fibrates and niacin
Fat catabolism
• Ketosis
• Excessive leads to metabolic acidosis
• FA catabolized into ketone bodies two carbons
at a time – ß - oxidation
Body Temperature: Energy Balance in the Body
ENERGY INPUT
DIET
• Hunger/appetite
• Satiety
• Social and
psychological
factors
ENERGY OUTPUT
HEAT (~50%)
• Unregulated
• Thermoregulation
WORK (~50%)
• Transport across membranes
• Mechanical work
Movement
• Chemical work
• Synthesis for growth and
maintenance
• Energy storage
• High-energy phosphate
bonds (ATP,
phosphocreatine)
• Chemical bonds
(glycogen, fat)
Figure 22-18
Body Temperature: Heat Balance in the Body
EXTERNAL HEAT INPUT + INTERNAL HEAT PRODUCTION = HEAT LOSS
Evaporation
Radiation
Radiation
heat input
Conduction
Body heat
heat loss
Conduction
Convection
Internal
heat
production
heat production
From
From muscle
metabolism contraction
“Waste ? Nonshivering
Shivering
“Waste
heat” thermogenesis thermogenesis heat”
Regulated processes
for temperature homeostasis
Figure 22-19
Body Temperature: Thermoregulatory Reflexes
Figure 22-20 (1 of 2)
Body Temperature: Thermoregulatory Reflexes
Figure 22-20 (2 of 2)
Mechanisms of Body Temperature Regulation
• Neural control of cutaneous blood flow alters
heat loss through the skin
• Sweat contributes to heat loss
• Heat production
• Voluntary muscle contraction and normal
metabolism
• Regulated heat production
• Shivering versus nonshivering thermogenesis
Homeostatic Responses to High Temperature
Figure 22-21 (1 of 2)
Homeostatic Responses to Low Temperature
Figure 22-21 (2 of 2)
Regulation of Body Temperature
• Our hypothalamic thermostat can be reset
• Typical physiological variations
• Fever occurs when pyrogens reset the thermostat
• Pathological cases of altered body temperature
• Hyperthermia - compare
• Heat exhaustion
• Heat stroke
• Heat exhaustion is characterized by significant sweating, loss
of color, cramps, fatigue, fainting and dizziness.
• Heat stroke symptoms include a body temperature over 103,
dry skin, high heart rate, confusion and even unconsciousness
• Malignant hyperthermia
• Hypothermia
• Diving reflex √
Summary
• Appetite and Satiety
• Feeding and satiety centers, glucostatic versus
lipostatic theories, regulation of food intake by
numerous regulatory peptides
• Energy Balance
• Definition of energy balance, bodily uses for
energy, direct calorimetry, oxygen consumption,
RQ, RER, BMR, diet-induced thermogenesis,
glycogen and fat as two major forms of stored
energy
Summary
• Metabolism
• Anabolic pathways versus catabolic pathways,
fed state versus fasted state, glycogenesis,
glycogenolysis, and gluconeogenesis
• Chylomicrons, lipoprotein lipase, apoproteins A
and B, LDL-C, risks factors for heart disease,
beta oxidation and ketone bodies
Summary
• Homeostatic Control of Metabolism
• Ratio of insulin to glucagon, Islets of
Langerhans, insulin-receptor substrates, major
targets and effects of insulin, glucagon and the
fasted state, diabetes mellitus, and metabolic
syndrome
• Regulation of body temperature
• Hypothalamic thermostat, routes and
mechanisms of heat loss, shivering
thermogenesis and nonshivering thermogenesis