PANCREATIC DISORDERS Flashcards
Which pancreatic cells perform an exocrine function?
Acini
Which pancreatic cells perform an endocrine function?
Islets
Which pancreatic islet cells secrete glucagon, and how are they stimulated?
Alpha cells, stimulated by hypoglycemia
What is action and target tissues of glucagon?
Promotes gluconeogenesis and glycogenolysis in the liver
Which pancreatic islet cells secrete insulin, and how are they stimulated?
Beta cells, mainly stimulated by increased blood sugar
Also stimulated by increased glucagon, increased cortisol, certain amino acids, and vagal stimulated (i.e. anticipation of food)
What is the action and target tissues of insulin?
Decreases blood sugar by increasing the expression of insulin-dependent glucose transporters (GLUT4) on skeletal muscle and adipose tissue
What are 5 steps to insulin release?
- Glucose enters beta cells through glucose transporter
- Glucose transformed into ATP
- Closes K+ channels, depolarizes cell
- Ca2+ channels open, trigger insulin release
- 1st phase: stored insulin, 2nd phase: newly synthesized insulin
What hormone do delta islet cells secrete, and what is its function?
Somatostatin, inhibits insulin & glucagon
What hormone do F islet cells secrete, and what is its function?
Pancreatic polypeptide, inhibits somatostatin
Name 5 hormones that increase blood sugar, and 1 hormone that decreases blood sugar
Increase:
1. Growth hormone
2. Catecholamines (e.g. epinephrine)
3. Glucagon
4. Thyroid hormone (T3/T4)
5. Glucocorticoids (e.g. cortisol)
Decrease:
1. Insulin
What are 2 possible causes for hyperinsulinism?
- Congenital islet cell hyperplasia
- Beta cell tumours (insulinomas)
Why do common symptoms of hyperinsulinism include excess sweating, palpitations, nervousness, and decreased LOC?
Symptoms of hypoglycemia
What is an experimental treatment for type 1 diabetes?
Islet cell transplant
How does obesity lead to type 2 diabetes?
Elevated triglycerides interrupt insulin signaling
Name 3 examples of genetic defects that can lead to type 2 diabetes
- Decreased number of insulin receptors on target cells
- Insulin does not cause insertion of GLUT4
- Defective GLUT4
Name 3 reasons why insulin secretion may be impaired, leading to type 2 diabetes
- Abnormal insulin production
- Glucotoxicity: glucose accumulation in beta cells causes apoptosis
- Lipotoxicity: elevated triglycerides creates inflammation, damaging beta cells
What are 2 actions of biguanides and thiazolidinediones?
- Increase glucose uptake
- Inhibit gluconeogenesis
What is the action of secretagogues like sulfonylureas and meglitinides?
Stimulate insulin release
What is the action of alpha-glucosidase inhibitors?
Inhibit carbohydrate digestion and absorption
What is the action of gliflozins?
Inhibit reabsorption of glucose in the kidneys
What are 4 examples of drugs that antagonize insulin, which can lead to secondary diabetes?
- Glucocorticoids
- Adrenergic agonists
- Thiazide diuretics
- Atypical antipsychotics
What are 4 examples of endocrine disorders that could lead to secondary diabetes?
- Cushing’s (hypercortisolism)
- Acromegaly (growth hormone excess)
- Hyperthyroidism
- Pheochromocytoma (catecholamine excess)
Why do some women develop diabetes while pregnant?
Hormones of pregnancy create a state of insulin resistance
How does placental lactogen antagonize insulin?
- Mobilizes lipids (gluconeogenesis)
- Decreases maternal glucose use to meet needs of fetus
What test is used to screen pregnant women for gestational diabetes?
Oral glucose tolerance test at 24-28 weeks
Diabetic ketoacidosis is typically seen in which type of diabetes?
Type 1
Explain how type 1 diabetes can lead to severe dehydration
- Insulin deficiency causes unopposed glucagon activity
- Hyperglycemia
- Osmotic diuresis
- Dehydration
Explain how type 1 diabetes leads to ketonemia
- Insulin deficiency means the body cannot utilize glucose
- Activation of lipoprotein lipase
- Breakdown of adipose tissue
- Fatty acids metabolized to ketone bodies
Ketonemia and severe dehydration creates what state?
Metabolic acidosis
Which 4 compensatory mechanisms are activated in metabolic acidosis?
- Polydipsia
- Polyphagia
- Tachycardia
- Hyperventilation
Which substance is used to reduce acidity in patients with diabetic ketoacidosis?
Bicarbonate
How is hyperglycemia hyposmolar state similar/different from DKA?
Similar:
1. Severe dehydration
Different:
1. No ketoacidosis as there is sufficient insulin to prevent lipolysis
- More gradual onset
Name 3 mechanisms behind chronic complications of diabetes
- Protein glycation
- Glucose accumulation in non-GLUT4 cells
- Protein kinase C activiation
What is the end product of protein glycation?
Advanced glycation end products (AGEs)
What effect does protein glycation have on the immune system?
AGEs stimulate macrophages to release inflammatory cytokines, growth factors, and reactive oxygen species
What effect does protein glycation have on the cardiovascular system?
- Causes atherosclerosis
- Destroys microvasculature
In what kind of cells does glucose accumulate in as a complication of diabetes?
Cells that do not require insulin for glucose uptake, e.g. nerves, blood vessels, the lens of the eye
How does glucose accumulation in non-GLUT4 cells cause cellular injury?
- Glucose is metabolized into sorbitol and fructose
- Increased intracellular osmolarity
- Influx of water into cells, cell swelling
How does chronic hyperglycemia disrupt antioxidant pathways?
- Glucose metabolism requires NADPH, an anabolic cofactor
- NADPH is also required to create the antioxidant glutathione
- NADPH is depleted due to excess glucose metabolism
- Decreased glutathione levels, reducing body’s antioxidant capacity
What is protein kinase C?
A family of enzymes that trigger enzyme cascades
What are 5 ways that activation of protein kinase C leads to chronic complications of diabetes?
- Pro-angiogenesis > retinopathy
- Inactivation of the vasodilator eNOS > hypertension
- Increased pro-fibrogenic molecules > fibrotic depositions outside cells
- Increased pro-coagulant molecules > thrombosis
- Increased inflammatory cytokines
What is the key cause of diabetic nephropathy?
Ischemia damages glomeruli
What is the term for hardening of the glomerular basement membrane in diabetic nephropathy?
Glomerulosclerosis
What causes albuminuria in diabetic nephropathy?
Increased permeability of glomerular capillaries
What are 3 consequences of diabetic nephropathy?
- Pyelonephritis
- CKD
- Uremia
What are 2 kinds of neuropathy?
- Somatic neuropathy
- Autonomic neuropathy
Why does neovascularization cause diabetic retinopathy?
The new vessels are abnormal and leaky
What are 3 consequences of diabetic retinopathy?
- Retinal detachment
- Glaucoma
- Cataract formation
How may diabetic vascular disease affect the GI system?
Ischemic gastroenteropathy (necrotic bowel)
What causes immunodeficiency in diabetics?
Chronic inflammation and vascular damage impairs the immune system
