1. FUNCTION/DYSFUNCTION OF ENDOCRINE PANCREAS
Diabetes

2. Anatomy of the pancreas:
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

5. 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

8. 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

9. 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

10. 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.

11. Insulin secretion is decreased by:
Decreased blood glucose concentration
Increased blood insulin concentration
Sympathetic stimulation

12. 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

13. 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.

14. 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

15. Diabetes mellitus Excessive thirst = polydipsia
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

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

17. Type 1 or IDDM 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

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

20. Clinical Manifestations:
Glucose in urine- Because when insulin is not present, glucose is not taken up out of the blood at the target cells.
So blood glucose is very highly increased → increased glucose filtered and excreted in the urine (exceeds transport maximum)

21. Clinical Manifestations:
Weight loss - Patient eats, but nutrients are not taken up by the cells and/or are not metabolized properly
Osmotic diuresis results in fluid loss
Loss of body tissue by metabolism of fats and proteins

22. 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

23. Treatment 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

24. 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

25. 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

26. Other:
Pancreatic transplant – so far not successful
Experimental therapies – not as successful as hoped

27. 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

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

29. These effects may be due to:
Abnormally functioning β cells
Decreased β cell mass,
or a combination of the two
3. Target cell resistance to insulin
Due to:
Decreased number of insulin receptors
Postreceptor events may be responsible
Cells “burn out” and become insensitive

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

31. Treatment 2. Appropriate diet (see IDDM above) 3. Sulfonyl ureas
1. Weight loss
2. Appropriate diet (see IDDM above)
3. Sulfonyl ureas
stimulate β cells to increase insulin secretion
Works only when β cells are still functioning
→ An enhancement of insulin’s effect at target cells
4. Exercise - promotes weight loss

32. Gestational Diabetes
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

33. 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

34. Treatment :
provide glucose (I.V. or subcutaneous if unconscious)
Observe for relapse

35. 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 
Increased ketones in blood
Acid/base imbalance
Polyuria, dehydration Electrolyte disturbances
Hyperventilation (Kussmaul – deep, gasping)
CNS effects
Acetone on breath

36. Treatment:
‑ low dose insulin
Also, administer fluids, electrolytes

37. 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

38. 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

39. In the eye – the retina is metabolically quite active, so hypoxia here is a big problem
So see:
Retinal ischemia→
Formation of microaneurisms, hemorrhage, tissue infarct, formation of new vessels, retinal detachment

43. In the kidney – diabetes is the most common cause of end‑stage renal disease
Injured glomeruli (glomerulosclerosis)
In these patients, see:
Proteinuria (protein is excreted into the urine) → Generalized body edema, hypertension

44. 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
why diabetic patients face problems with their lower legs and feet
Increased risk of infections