Insulin and Diabetes Meliitus, endokrinologi.ppt

DM

1. Endocrine Physiology
Ns. Kharisma Pratama, MNS

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Function - Dysfunction of
Endocrine Pancreas
(Diabetes)

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Both an exocrine and endocrine organ.
Cells with exocrine function release an
alkaline fluid containing sodium
bicarbonate and enzymes →
pancreatic duct → small intestine.
Pancreatic “juice” aids in breakdown
and digestion of food in the small
intestine.
Pancreatic exocrine cells = acinar cells.
Anatomy of the pancreas:

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Endocrine Function
oCells of the Islet of Langerhans
synthesize and release hormones into the
circulation.
oHormones travel through the
bloodstream to target tissues (especially
liver and muscle).
oAt the target cells, hormones bind specific
receptors and cause cell changes that
control metabolism.

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Pancreatic endocrine cells regulate
carbohydrate, fat, protein metabolism

Alpha cells – secrete the hormone
glucagon.

Beta cells – secrete the hormones
insulin and amylin.

Delta cells – secrete the hormones
gastrin and somatostatin.

F cells – secrete hormone pancreatic
polypeptide.

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Beta Cells

Synthesize pre-proinsulin, a protein.
This is cleaved by enzymes
→proinsulin, then cleaved again →
insulin.

Insulin is the biologically active
hormone that is released into the
bloodstream.

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Insulin secretion is controlled
through several mechanisms:

Chemically – high levels of glucose and
amino acids in the blood.

Hormonally – beta cells are sensitive to
several hormones that may inhibit or
cause insulin secretion.

Neurally – stimulation of the
parasympathetic nervous system
causes insulin to be secreted.

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Insulin secretion is decreased by:
Insulin secretion is decreased by:
•Decreased blood glucose
concentration.
•Increased blood insulin concentration.
•Sympathetic stimulation.
The decrease in insulin secretion
is an adaptive mechanism of the body to maintain blood glucose balance
and ensure that energy is available according to needs.

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Insulin

Transported through the blood to target tissues where
it binds to specific receptors.

The binding of insulin to target cells:

Acts as a biochemical signal to the inside of the cell.

Overall, cell metabolism is stimulated.

There is increased glucose uptake into the cell.

Regulation of glucose breakdown within the cell.

Regulation of protein and lipid breakdown within
the cell.

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
Blood glucose is decreased because
insulin causes glucose to leave the
bloodstream and enter the
metabolizing cells.

With the exception of brain, liver and
erythrocytes, tissues require membrane
glucose carriers.

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Disorder ‑ Diabetes mellitus

The single most common endocrine
disorder – group of glucose
intolerance disorders.

Incidence is estimated at 1-2% of the
North American population.

Many of these cases are
undiagnosed.

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Diabetes mellitus
 Historically ‑ distinguished by weight loss,
excessive urination, thirst, hunger:
Excessive urination= Polyuria
Excessive thirst = Polydipsia
Excessive hunger = Polyphagia
Modern characterization is by
hyperglycemia and other metabolic
disorders.

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Modern classifications

Type 1 or IDDM ‑ Insulin Dependent
Diabetes Mellitus.

Type 2 or NIDDM ‑ Non‑Insulin Dependent
Diabetes Mellitus.

GDM ‑ Gestational Diabetes Mellitus.

Other Types of Diabetes Mellitus.

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
Accounts for 10% all DM in the Western
world ~10-15% have parent or sibling with
the disease. Peak age of diagnosis = 12
years.

Genetic/environmental/autoimmune factors
destroy beta cells.

Believed abrupt onset – now
immunomarkers and preclinical symptoms
have been discovered.
Type 1 or IDDM

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
Disequilibrium of hormones produced by
islets of Lagerhans : low insulin and high
glucagon.

Ratio insulin/glucagons apparently
controls metabolism of glucose and fats.

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Clinical Manifestations
Glucose in urine:
-Because when insulin is not present,
glucose is not taken up out of the blood
at the target cells.
-Blood glucose is very highly increased →
increased glucose filtered and excreted in
the urine (exceeds transport maximum).
-Weight loss - Patient eats, but nutrients
are not taken up by the cells and/or are
not metabolized properly.

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Clinical Manifestations (Cont.)
-Osmotic diuresis results in fluid loss.
-Loss of body tissue by metabolism of fats
and proteins.
-Polyuria, polydipsia, pholyphagia,
Ketoacidosis:

Fats and proteins are metabolized
excessively, and byproducts known as
ketone bodies are produced. These are
released to the bloodstream and cause:

Decreased pH (so increased acidity).

Compensations for metabolic acidosis.

Acetone given off in breath.

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Type 2 or NIDDM

More common than IDDM, often
undiagnosed.

It has a slow onset.

Most common in those >40 years, though
children are being diagnosed more
regularly.

May be genetic .

Obesity is the greatest risk factor for
this disease, and is related to increased
incidence in children.

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
NIDDM → insulin resistance in target
cells.

See decreased β cell responsiveness →
Decreased insulin secreted by β
cells.

Also abnormal amount of glucagon
secreted.

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These effects may be due to:
1. Abnormally functioning β cells.
2. Decreased β cell mass.
3. Or a combination of both 1 and 2.
4. Target cell resistance to insulin, Due to:
1) Decreased number of insulin receptors.
2) Postreceptor events may be
responsible.
3) Cells “burn out” and become
insensitive.

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
Overweight, hyperlipidemia common
(but these are precursors, not
symptoms).

Recurrent infections.

Visual changes, paresthesias, fatigue.
Clinical manifestations

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•Due to increased hormone secretion
during pregnancy.
•Seen if patient has predisposition.
•If previous or potential glucose
intolerance has been noted.
•Important ‑ increased mortality risk for
mother, child
Gestational Diabetes

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Complications of Diabetes Mellitus
Acute:

Hypoglycemia = rapid decrease in plasma
glucose = insulin shock.

Neurogenic responses – probably due to
decreased glucose to hypothalamus.

Symptoms include:
-Tachycardia, palpitations, tremor, pallor .
-Headache, dizziness, confusion.
-Visual changes.

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Ketoacidosis: Involves a precipitating event:
-Increased hormones released w/ trauma 
increased glucose produced by the body’s cells.
-This “antagonizes” the effects of any glucose
present, which leads to :
•Increased ketones in blood.
•Acid/base imbalance.
•Polyuria, dehydration.
•Electrolyte disturbances.
•Hyperventilation.
•CNS effects.
•Acetone on breath.

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Chronic Complications of DM
Neuropathies = nerve dysfunctions →
slowing of nerve conduction. In these
patients, see:
-Degeneration of neurons →Sensory,
motor deficits →Muscle atrophy,
paresthesias.
-Depression.
-G.I. problems, as muscle motility
decreased.
-Sexual dysfunction.

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
Microvascular disease:
-Chronic diabetes w/ improper glucose
metabolism → thickening of the
basement membrane of capillaries,
particularly in the eye and the kidney.
-As the capillary changes in this way, →
Decreased tissue perfusion.
-So ischemia → hypoxia.

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In the eye:
-The retina is metabolically quite active, so
hypoxia here is a big problem .
-So, the following events can be seen:
•Retinal ischemia →
•Formation of microaneurisms, hemorrhage,
tissue infarct, formation of new vessels,
retinal detachment.

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In the kidney:
-Diabetes is the most common cause
of end ‑ stag renal disease.
-Injured glomeruli (glomerulosclerosis)
In these patients, the following
signs can be seen:
•Proteinuria (protein is excreted into
the urine) → Generalized body
edema, hypertension.

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Macrovascular disease:
-Atherosclerosis .
-Plaque formation increases → Increased
risk of coronary artery disease, so
increased risk of myocardial infarction.
-Increased risk of congestive heart
failure.
-Stroke.
-Peripheral vascular disease, that’s why
diabetic patients face problems with
their lower legs and feet.
-Increased risk of infections.