FUNCTION/FUNCTION/DYSFUNCTION OF DYSFUNCTION OF ENDOCRINE ENDOCRINE PANCREAS PANCREAS DiabetesDiabetes

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Anatomy of the pancreas:

Both an exocrine and endocrine organCells 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

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Endocrine Function :Cells of the Islet of Langerhans synthesize and release hormones into the circulation.

Hormones travel through the bloodstream to target tissues (especially liver and muscle)

At the target cells, hormones bind specific receptors and cause cell changes that control metabolism

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Pancreatic endocrine cells regulate Pancreatic endocrine cells regulate carbohydrate, fat, protein metabolism:carbohydrate, fat, protein metabolism:– Alpha cellsAlpha cells – secrete the hormone – secrete the hormone

glucagon (opposite function as glucagon (opposite function as insulin)insulin)

– Beta cellsBeta cells – secrete the hormones – secrete the hormones insulin and amylin (similar function insulin and amylin (similar function as insulin)as insulin)

– Delta cellsDelta cells – secrete the hormones – secrete the hormones gastrin and somatostatingastrin and somatostatin

– F cellsF cells - secrete hormone - secrete hormone pancreatic polypeptidepancreatic polypeptide

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Beta CellsBeta Cells

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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

Insulin secretion is Insulin secretion is controlled through several controlled through several mechanisms:mechanisms: ChemicallyChemically – high levels of glucose – high levels of glucose

and amino acids in the bloodand amino acids in the blood HormonallyHormonally – beta cells are – beta cells are

sensitive to several hormones that sensitive to several hormones that may inhibit or cause insulin secretionmay inhibit or cause insulin secretion

NeurallyNeurally – stimulation of the – stimulation of the parasympathetic nervous system parasympathetic nervous system causes insulin to be secreted.causes insulin to be secreted.

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Insulin secretion is Insulin secretion is decreased by:decreased by:

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• Decreased blood glucose concentration• Increased blood insulin concentration• Sympathetic stimulation

InsulinInsulin Transported through the blood to target tissues Transported through the blood to target tissues

where it binds to specific receptorswhere it binds to specific receptors The binding of insulin to target cells:The binding of insulin to target cells:

– Acts as a biochemical signal to the inside of the Acts as a biochemical signal to the inside of the cellcell Overall, cell metabolism is stimulatedOverall, cell metabolism is stimulated There is increased glucose uptake into the cellThere is increased glucose uptake into the cell Regulation of glucose breakdown within the cellRegulation of glucose breakdown within the cell Regulation of protein and lipid breakdown Regulation of protein and lipid breakdown

within the cellwithin the cell

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Blood glucose is decreased because Blood glucose is decreased because insulin causes glucose to leave the insulin causes glucose to leave the bloodstream and enter the bloodstream and enter the metabolizing cells.metabolizing cells.

With the exception of brain, liver and With the exception of brain, liver and erythrocytes, tissues require erythrocytes, tissues require membrane glucose carriers.membrane glucose carriers.

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Disorder ‑ Diabetes mellitusDisorder ‑ Diabetes mellitus

The single most common The single most common endocrine disorder – group of endocrine disorder – group of glucose intolerance disordersglucose intolerance disorders

Incidence is estimated at 1-2% of Incidence is estimated at 1-2% of the North American populationthe North American population

Many of these cases are Many of these cases are undiagnosedundiagnosed

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Diabetes mellitusDiabetes mellitus

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Historically ‑ distinguished by weight loss, excessive urination, thirst, hunger

Excessive urination = polyuriaExcessive thirst = polydipsiaExcessive 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

Type 1 or IDDMType 1 or IDDM

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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

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Imbalance of hormones produced by islets of Lagerhans : low insulin and high glucagon

Clinical Manifestations:Clinical Manifestations:Glucose in urine- Glucose in urine- Because when Because when

insulin is not present, glucose is not insulin is not present, glucose is not taken up out of the blood at the taken up out of the blood at the target cells.target cells.

So blood glucose is very highly So blood glucose is very highly increased increased →→ increased glucose increased glucose filtered and excreted in the urine filtered and excreted in the urine (exceeds transport maximum)(exceeds transport maximum)

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Clinical Manifestations:Clinical Manifestations:Weight loss - Weight loss - Patient eats, but Patient eats, but

nutrients are not taken up by the nutrients are not taken up by the cells and/or are not metabolized cells and/or are not metabolized properlyproperly

Osmotic diuresisOsmotic diuresis results in fluid loss results in fluid loss

Loss of body tissue by metabolism of Loss of body tissue by metabolism of fats and proteinsfats and proteins

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Fats and proteins are metabolized excessively, and byproducts known as ketone bodies are produced. These are released to the bloodstream and cause:

Decreased pH (increased acidity), metabolic acidosis

Acetone given off in breath

TreatmentTreatment

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1. Administer insulin

May be of animal or human origin

Cannot be given orally

Patient must monitor their blood glucose concentration and administer insulin

with the correct timing

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2. Control diet

Carbohydrates should make up about 55-60% of patient’s total calories

Fats should make up <30% of patient’s total calories

Proteins should make up about 15-20% of patient’s total calories

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3. Monitor exercise

Remember: muscles are a target tissue of insulin, and metabolize much glucose for energy

Sometimes exercise →irregular blood glucose levels So diabetic patients should be monitored when they are exercising

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Other:

Pancreatic transplant – so far not successfulExperimental therapies – not as successful

as hoped

Type 2 or NIDDMType 2 or NIDDM

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More common than IDDM, often undiagnosedIt has a slow onsetMost common in those > 40 years, though

children are being diagnosed more regularly

May be genetic Obesity is the greatest risk factor for this

diseaseAnd is related to increased incidence in

children

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NIDDM → insulin resistance in target cellsdecreased β cell responsiveness →

Decreased insulin secreted by β cellsAlso abnormal amount of glucagon secreted

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These effects may be due to:

1.Abnormally functioning β cells2. Decreased β cell mass, or a combination

of the two3. Target cell resistance to insulin

Due to:Decreased number of insulin receptors Postreceptor events may be responsibleCells “burn out” and become insensitive

Clinical manifestationsClinical manifestations

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Overweight, hyperlipidemia common (but these are precursors, not symptoms)

Recurrent infections

Visual changes, paresthesias, fatigue

TreatmentTreatment

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1. Weight loss2. Appropriate diet (see IDDM above)3. Sulfonyl ureas

stimulate β cells to increase insulin secretionWorks only when β cells are still functioning

→ An enhancement of insulin’s effect at target cells

4. Exercise - promotes weight loss

Gestational DiabetesGestational Diabetes

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Due to increased hormone secretion during pregnancy

Seen if patient has predispositionIf previous or potential glucose intolerance has been noted

Important ‑ increased mortality risk for mother, child

Complications of Diabetes Complications of Diabetes MellitusMellitus

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Acute:Hypoglycemia = rapid decrease in plasma

glucose = insulin shockNeurogenic responses – probably due to

decreased glucose to hypothalamus.Symptoms include:

Tachycardia, palpitations, tremor, pallorHeadache, dizziness, confusionVisual changes

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Treatment :

provide glucose (I.V. or subcutaneous if unconscious)

Observe for relapse

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Ketoacidosis – involves a precipitating event:Increased hormones released w/ trauma

increased glucose produced by the body’s cellsThis “antagonizes” the effects of any glucose

present Increased ketones in blood

Acid/base imbalancePolyuria, dehydration

Electrolyte disturbancesHyperventilation (Kussmaul – deep, gasping)

CNS effectsAcetone on breath

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Treatment: ‑ low dose insulin

Also, administer fluids, electrolytes

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Chronic Complications of DMNeuropathies = nerve dysfunctions →

slowing of nerve conduction.

In these patientsDegeneration of neurons →Sensory, motor deficits →Muscle atrophy, paresthesias

G.I. problems, as decreased muscle motility

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

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‑stage renal diseaseInjured glomeruli (glomerulosclerosis)

In these patients

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 infarctionIncreased risk of congestive heart failureStrokePeripheral vascular disease

diabetic patients face problems with their lower legs and feet

Increased risk of infections