Control of Blood Glucose

The Body Alternates Between Anabolic &

Catabolic States

Anabolism: energy storage & growth

Catabolism: mobilization of stored energy to support

body functions

We use energy continuously but take it in only during

meals

During and immediately following a meal the body

goes into an anabolic state & stores energy:

Anabolic activities are supported by the hormone

insulin

Between meals the body goes into the state of

catabolism: it breaks down glycogen, triglycerides

and sometimes protein to provide energy

Catabolism is supported by the hormones glucagon

and growth hormone

In exercise or stressful situations epinephrine and

cortisol increase the rate of catabolism

The Brain Requires Blood Glucose

The brain is the organ most sensitive to glucose

Brain requires a constant supply of blood glucose

Normally glucose is the only energy source for

the brain (can't use fats)

In starvation brain will adapt to use some

ketones

Hypoglycemia = low blood glucose; sometimes

caused when diabetic takes too much insulin

(insulin shock)

Symptoms: mental confusion, slurring of speech -

> coma -> death

Treatment: give glucose

Blood Glucose is Controlled Mainly by the Liver

Immediately after meals blood glucose comes from

meal

Between meals blood glucose comes from the liver

& kidneys

Only the liver and kidneys can release glucose

into the blood (requires a special enzyme that

converts glucose metabolites to glucose, which

can be transported across the cell membrane)

Liver provides 80% of blood glucose supply

between meals, the kidney 20%

Liver makes glucose in 2 ways:

Breaks down liver glycogen (glycogenolysis)

Converts other types of small molecules into

glucose (gluconeogenesis)

Gluconeogenesis requires 4 special enzymes

which can reverse some of the reactions of

glycolysis

Many small molecules can be converted to

glucose:

Lactate & pyruvate: mainly come from muscles

Glycerol: supplied by adipose tissue when

triglycerides are broken down-

Fatty acids cannot be converted into

glucose, but:

Fatty acid metabolism indirectly supports

gluconeogenesis by producing AcetylCoA.

Amino acids: 20 of the 22 amino acids can be

converted to glucose

Figure shows rate of glucose delivery to the blood by

the liver.

Delivery of glucose to the blood is controlled by

insulin, glucagon and other hormones

Brain receives a constant 80 mg/min (doesn't change

much in exercise)

Amount delivered to other tissues depends upon

body state (rest vs exercise)

At rest total glucose output to the blood is about

130 mg/min (80 to brain, 50 to other tissues)

During exercise total can increase to about 2500

mg/min

The Only Hormone that Can Lower Blood Glucose is Insulin

Muscle, fat and liver tissues require insulin to transport insulin

into the cells; in these tissues insulin seems to increase the

number of glucose transporters in the cell membrane

Many other tissues, including brain, do not require insulin to

transport glucose

Insulin also increases activity of enzymes that cause storage of

sugar as glycogen or lipid

After a meal blood sugar rises and this stimulates the release of

insulin from the pancreas;

Extra insulin then causes the sugar to enter the cells and

become stored

Both Insulin and Glucagon are Made in the

Endocrine Part of the Pancreas

The pancreas has both an exocrine and endocrine

part

Endocrine part: small clumps of cells called islets

of Langerhans

Exocrine part: makes digestive enzymes.

If blood sugar is high secretes large amounts of

insulin, small amounts of glucagon

Secretion reversed when blood sugar is low

Glucagon raises blood sugar, insulin lowers it

Several Hormones Can Raise Blood Glucose

Four major hormones raise blood glucose:

Glucagon

Cortisol

Epinephrine

Growth hormone

In vigorous exercise all 4 of these hormones increase

Diabetes Mellitus Results When Insulin is Deficient or

Ineffective

Diabetes = excess production of urine

Mellitus = sweet (refers to sugar in urine)

Two types of diabetes mellitus:

Type I: autoimmune destruction of pancreatic cells, usually

occurs early in life. Characterized by low insulin output, high

blood glucose, glucose in urine, excess urine flow, switch to

fat metabolism. Treated with insulin injections, careful balance

of diet & exercise.

Type II: associated with obesity, usually starts later in life.

Insulin may be normal, but is ineffective (insulin resistance).

Many of symptoms the same, but less severe. May be

reversed if weight is lost. Cause unknown.

Gestational Diabetes

• Pregnant women have a higher insulin

level.

• If woman has hyperglycemia, her blood

glucose crosses the placenta but her

insulin does not.

• This can cause a high birth weight for

baby.

If Blood Sugar is Too High Some Will Spill Into the

Urine

Kidney filters glucose into tubules and then reabsorbs

it (100% in normal person)

If glucose concentration is too high reabsorption

cannot keep up with filtration and some glucose stays

in tubule and becomes part of urine

Glucose in the urine will suck more water into the urine

(osmosis) and cause excess urine production

(diabetes); body will be dehydrated -> thirst

Urine glucose test useful in diagnosing diabetes

Measured with Benedict's reagent or glucose

oxidase enzyme

What are the Symptoms?

• Polyphasia- excessive eating

• Polyurea- excessive urination

• Polydypsia-excessive fluid intake

• Blurred vision

• Poor wound healing

• Irritability

Diabetes is Sometimes Called "Starvation in the Midst of

Plenty"

A diabetic has plenty of sugar in his blood but many of his tissues

cannot use it because it can't get into the cells

Glucose is water soluble and cannot cross cell membranes by

simple diffusion

A series of procedures move glucose across membranes

Insulin stimulates sugar transport into muscle, and fat cells (but

not into brain cells)

Causes insertion of GLUT4 transport molecules into

membranes of muscle and adipose tissue

Brain has its own transporter, GLUT3; not insulin dependent

In diabetes cells must look for alternate sources of energy

When the Body Can't Burn Glucose it Switches to

Fat Metabolism

If muscle cells can't get enough glucose body will

increase fat breakdown to provide free fatty acids

(FFAs) as an energy source

Remember: brain cannot use FFAs

A side reaction of excess lipid metabolism is the build-

up of ketoacids in the blood

Ketoacids can be smelled on breath: odor similar to

acetone

Ketoacids disturb mental functions and lower blood

pH

Diabetics May Have Poor Circulation

Excess sugar makes the blood syrupy (more

viscous): harder for heart to pump

Excessive urine flow dehydrates body, reduces

blood volume

Both effects reduce the circulation

Diabetic Ketoacidosis is a Medical Emergency

If a diabetic lets his blood sugar get too high he may

develop ketoacidosis, a life-threatening emergency

Most of the problems in ketoacidosis are due to:

Dehydration (due to excessive urine production)

Low pH (due to excessive lipid metabolism)

Large amounts of ketoacids in the blood (also due

to excessive lipid metabolism)

Diagnosis contd.

• In order to be diagnosed with diabetes:

• Person must have symptoms of

diabetes +

• Causal plasma glucose >200

• Fasting blood glucose of >126 mg/dl

• 2-hour plasma glucose >200 mg/dl on

oral glucose test

Blood Glucose Monitoring

• All diabetics must keep track of blood

glucose levels.

• This is the only way to know if the treatment

is effective.

• Gives the diabetic a good indication of what

affects their blood sugar level.

• Must check at least 2 times a day and four

times a day for at least 3 days a week.

Hemoglobin A1c

• A good indicator of blood glucose

control.

• Gives a % that indicates control over

the preceding 2-3 months.

• Performed 2 times a year.

• A hemoglobin of 6% indicates good

control and level >8% indicates action

is needed.

Who’s at risk?

It is now recommended that screening

for diabetes should be considered for all

patients at age 45. If the results are

normal it should be repeated every 3

years.

Screening should be considered at a

younger age if patient meets following

risk factors:

Who’s at risk?

• Obesity

• First degree relative with diabetes

• Belongs to a high-risk ethnic group

• Was diagnosed with gestational

diabetes or delivered a baby whose

birth weight >9 lbs.

• Hypertension

Who’s at risk?

• HDL level<35 or triglycerides >250

• Found to have impaired glucose

tolerance or impaired fasting on a

previous test.