APPP 08 and 13: Pancreas Flashcards
If diabetes is poorly treated, what are some of the serious consequences?
- renal failure
- blindness
- heart attack
- stroke
- end-limb amputation
Diabetes Prevalence Statistics
- global: around 463 million, projected to grow to 700 million by 2045
- Canada: over 11 million people with diabetes or pre-diabetes
- 75% of people with diabetes require hospitalization due to complications
What is insulin?
a hormone secreted from the islets of langerhans scattered throughout the pacreas
What are the 4 major cell types within the islets?
- beta-cells
- ?
What do beta-cells do?
(60-80% of all islets)
produce insulin and principally function as ‘fuel-sensors capable of adapting the rate of insulin secretion to variations in plasma levels of glucose
What does glucose do?
- most important controller of insulin secretion – increases the ATP/ADP ratio, closing the K+ channel, eliciting depolarization of the membrane, facilitating Ca2+ entry, and causing exocytosis of secretory granules containing insulin
- an initiator or primary stimuli able to increase insulin secretion in the absence of any other stimulatory agent
Can amino acids trigger insulin secretion?
yes
Can fatty acids trigger insulin secretion?
yes
How do sulfonylureas (ie. tolbutamide, glyburide) affect insulin secretion?
- block K+ channels by a direction action on a site located at or near the channel (sulfonylurea urea receptor or SUR)
- increase insulin secretion
How does glucagon-like peptide 1 (GLP-1) affect insulin secretion?
enhances secretion
How do catecholamines affect insulin secretion?
inhibits secretion
How does insulin action get initiated?
- synthesis in beta cells of the pancreas as proinsulin
- C-peptide (31 amino acid peptide that bridges the insulin A and B chains in the proinsulin molecule) is split off
- active form of the hormone consists of 51 amino acids in 2 chains – A chain with 21 amino acids, and B chain with 30 amino acids (both A and B chains are linked by disulfide bonds)
- (like all peptide hormones) insulin initiates its action by binding to a receptor on the cell surface, which leads to the generation of molecular signals that facilitate insulin action
What type of disorder is diabetes considered to be?
a metabolic disorder (carbohydrate, protein, fat)
- characterized by hyperglycemia and hyperlipidemia
What are the clinical manifestations of diabetes?
(the 3 P’s)
- polyuria
- polydypsia
- polyphagia
What does insulin do?
the principal messenger that facilitates the buildup of energy reservoirs (energy conserving hormone)
- promotes glycogen synthesis in the liver
- promotes muscle and lipid formation in adipocytes
- initiates amino acid uptake and protein synthesis in most cells
What is required for insulin to work?
cells must have enough receptors
Glucose Regulation
How does insulin regulate glucose?
- lowers plasma glucose levels by stimulating glucose uptake with the help of the glucose transporter GLUT4 in muscle and adipose tissue
- suppresses hepatic production of glucose
Glucose Regulation
What is responsible for glucose uptake?
- skeletal muscle is responsible for 80-85%
- adipocytes are responsible for 4-5%
Glucose Regulation
Describe glucose’s fate after entry into the cell?
- oxidative breakdown to produce energy
- conversion to glycogen for storage in the liver and muscle
- conversion to fats for storage in adipocytes
How does insulin regulate lipids?
can lower plasma triglyceride and fatty acid levels by multiple mechanisms:
- increase in glucose transport, which is then esterified to triglyceride
- inhibition of lipolysis
How does insulin regulate protein?
- increases the uptake of amino acids into many tissues (muscle, liver, adipose)
- stimulates protein synthesis
- inhibits protein degradation
What are the net effects of insulin? (4)
- decrease blood glucose
- decrease triglycerides and cholesterol
- decrease blood free fatty acids
- decrease blood amino acids
What are the 3 key functions of insulin?
- help blood sugar enter the body’s cells
- moderate the breakdown of the body’s reserves of carbohydrates, proteins, and fats
- inhibit glucose production in the liver
(by ‘putting the brakes’ on these processes, insulin keeps the body from becoming overloaded with breakdown products and/or glucose)
What is diabetes mellitus?
a metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion and/or defective insulin action (ie. increased resistance to insulin)
What is the primary manifestation of diabetes mellitus?
hyperglycemia (and other disturbances in fat and protein metabolism) can arise from various causes, with later manifestations like cardiovascular, neurological, ocular, and renal complications
What is type I diabetes?
consequence of an inability of the pancreas to produce insulin – absolute insulin deficiency
- around 10% of diagnosed cases of diabetes
- associated with deficient insulin secretion due to autoimmune pancreatic beta-cell destruction
What are people with type I diabetes prone to?
ketoacidosis
Is type I diabetes genetic or environmental?
- has genetic component
- environmental factors have also been suggested to initiate the autoimmune response – viruses (congenital rubella, Coxsackievirus B), cow’s milk, chemical toxins
What do type I diabetics depend on?
externally supplied insulin
- administered in the form of daily injections (syringes and needles, injection pens, or insulin pumps)
- most monitor their blood glucose at frequent intervals and adjust their insulin to the amount they plan to eat and exercise
Describe patients at presentation of type I diabetes.
- usually a rapid presentation of the disease with thirst, polyuria, weight loss, blurred vision, lethargy, and dizziness
- usually thin and ketotic
What is type II diabetes?
consequence of tissues (like skeletal muscle, adipose tissue, and liver) not responding to insulin
- around 90% of diagnosed cases
What are the 2 key factors that lead to type II diabetes?
- abnormalities in insulin action – body’s cells are unable to respond normally to insulin (ie. insulin resistance due to defects in insulin structure, insulin receptor, and glucose transporters)
- deficiency in insulin secretion – pancreas cannot secrete enough insulin in response to high blood glucose
(many diabetic patients demonstrate both insulin resistance and a deficiency in insulin secretion)