Endocrine - Pancreas Flashcards
What am I = ?
- Essential role in converting the food we eat into fuel for the body’s cells.
- Joined to the duodenum of small intestine, transporting digestive juices into the intestine.
Pancreas
Pancreas:
- Located posterior to the stomach in the upper left abdomen.
- Elongated flattened organ, about 6 inches long, extend horizontally across abdomen.
- Essential role in converting the food we eat into fuel for the body’s cells.
- Joined to the duodenum of small intestine, transporting digestive juices into the intestine.
- Are scattered throughout pancreas in spaces between the ducts = ?
Pancreas
(a) Endocrine gland releasing hormones…
- Pancreatic islets / islets of Langerhans which are scattered throughout pancreas in spaces between the ducts.
(b) Exocrine gland secreting digestive juices…
- Acinar cells =
- Ductal cells =
Endocrine cells of pancreas are arranged in clusters called = ?
* 4 cell types = ?
Pancreas
Pancreatic Islets:
(a) Endocrine cells of pancreas are arranged in clusters called islet of Langerhans.
- Composed of 1-2% of pancreatic mass.
- Approx. 1 million islet of Langerhans
(b) 4 Cell Types:
(1) β (beta) cells:
- Secrete insulin (60-80% in rodents and 50-70% in humans) (green).
(2) α (alpha) cells:
- Secrete glucagon (15-20%) (red)
(3) δ (delta) cells:
- Secrete somatostatin (5-10%) (blue)
(4) Remaining cells:
- Secrete pancreatic polypeptide (PP) or other peptides (not shown here) (5-10%)
Insulin is synthesized and secreted by = ?
- A-chain = ?
- B-chain = ?
Pancreas
Insulin:
- Insulin is synthesized and secreted by the β cells.
- Hormone of abundance; when excess nutrients in the body, insulin ensures that nutrients are stored as glycogen in liver, fat in adipose tissue and protein in muscle.
(b) Boosts an impressive array of “firsts”:
- First to be isolated from animal resources and administered therapeutically.
- First to have its structure and mechanism of action determined.
- A chain (21 amino acids)
- B chain (30 amino chains).
Synthesis of insulin = ?
Pancreas
Synthesis of insulin:
- Directed by chromosome 11
- Proinsulin (A and B chains of insulin and connecting peptide)
- Proinsulin is packed into secretory granules on Golgi apparatus cleave the connecting peptide, yielding insulin.
- Insulin + C peptide is packed in secretory granules, when beta cell is stimulated they are released in equimolar amounts.
Steps that regulate secretion of insulin = ?
Pancreas
Regulation of Insulin Secretion:
- Of all factors that affect secretion of insulin, glucose is most important, produced in the beta cells of pancreas.
- Insulin released into pancreatic blood and enters systemic circulation.
- C PEPTIDE secreted in equimolar amount with insulin and excreted unchanged in urine and used to asses and monitor endogenous β cell function
- C peptide is the basis of a test for β cells function in people with type 1 diabetes who are receiving injections of exogenous insulin.
- (1) Glucose enters the beta cell through GLUT2 transporters.
- (2) Glucokinase converts glucose into glucose-6-phosphate.
- (3) Glucose-6-phosphate undergoes oxidation in the mitochondria, which produces ATP.
- (4) Increased ATP closes ATP-sensitive potassium channels.
- (5) The closure of ATP-sensitive potassium channels leads to membrane depolarization.
- (6) Depolarization opens voltage-gated calcium channels.
- (7) Calcium enters the beta cell through the open voltage-gated calcium channels.
- (8) Increased intracellular calcium triggers the release of insulin from secretory vesicles via exocytosis.
Explain the effect of insulin on nutrient flow = ?
Pancreas
Effect of Insulin on Nutrient Flow:
(a) Decreases blood glucose levels
- Increases glucose transport into target cells like muscles, adipose tissue.
- Helps formation of glycogen from glucose.
- Inhibits gluconeogenesis (synthesis of glucose from other substances like amino acids).
(b) Decreases blood fatty acids and ketone concentrations.
- Increases the storage of fatty acids- decreases the circulation of fatty acids and ketoacids.
- In adipose tissue, stimulates fat deposition and inhibits lipolysis
(c) Decreases blood amino acid concentration.
- Increases amino acid and protein uptake by tissues, increases protein synthesis and inhibits protein degradation.
(d) Other actions:
- Ensures ingested K+ will be taken into cells
Action of Insulin
Pancreas
Action of Insulin
(a) Insulin helps to store excess nutrients in:
- Liver as glycogen
- Adipose tissue as fat
- Muscle as protein.
(b) These stored nutrients are available during subsequent periods of fasting to maintain glucose delivery to brain, muscle and other organs.
- Glycogenolysis: breakdown of glycogen to glucose.
- Gluconeogenesis: generation of glucose from non-carbohydrate carbon substrates.
- Lipolysis: breakdown of fats and other lipids
Glucagon = ?
Pancreas
Glucagon:
- Synthesized and secreted by α cells of the islet of Langerhans.
- Hormone of starvation
- Promotes mobilization and utilization of metabolic fuels: to maintain blood glucose concentration in the fasting state.
Action of Glucagon = ?
Pancreas
Action of Glucagon:
(a) Major action of glucagon are on liver
- Increased blood glucose concentration
- Glucagon stimulates glycogenolysis
- Inhibits glycogen formation from glucose
- Glucagon increases gluconeogenesis
(b) Increases blood fatty acid and ketoacid concentration
- Increases lipolysis, diverts substrates toward gluconeogenesis, ketoacids are produced from fatty acids.
Somatostatin = ?
Pancreas
Somatostatin:
(a) Secreted by δ cells of islet of Langerhans and also hypothalamus
(b) Action of somatostatin:
- Modulate or limit the response of insulin and glucagon to ingestion of food.
(c) Somatostatin is secreted in response to a meal, diffuses to nearby α and β cells and inhibits the secretion of insulin and glucagon.
(d) Inhibits the release of growth hormone, thyroid stimulating hormone, prolactin hormone.
Diabetes Mellitus = ?
Pancreas
Diabetes Mellitus:
(a) Diabetes is a chronic disease characterized by increased blood glucose levels (hyperglycemia) resulting from defects in insulin production, secretion or both.
- Disruption of metabolism of carbohydrate, proteins and fats.
Glucose Homeostasis = ?
Pancreas
Glucose Homeostasis:
Types of Diabetes = ?
Pancreas
Types of Diabetes:
(a) Type 1:
- Formerly called as Insulin Dependent Diabetes Mellitus; IDDM.
(b) Type 2:
- Formerly called as Non Insulin Dependent Diabetes Mellitus; NIDD.
Pathophysiology: Type 1 Diabetes
Pancreas
(a) Etiology
- Genetic
- Environmental (viruses, drugs/ toxins, stress)
(b) In the early stages of immune destruction, antibodies against beta cells are circulating, but hyperglycemia is not yet present - “prediabetes”.
- Prediabetes can last for years before hyperglycemia.
- Clinical manifestations when 80-90% of beta cell destruction.
Diabetic Ketoacidosis:
Pancreas
Diabetic Ketoacidosis:
- Ketoacidosis and metabolic derangement seen more with type 1 diabetes.
- Ketones - detected in blood and urine
- Produce more hydrogen ions- pH falls- metabolic acidosis- CNS depression- coma
- Protein catabolism - Diminish tissues ability to repair itself
Treatment of Type 1 Diabetes: Exogenous Insulin
Pancreas
Treatment of Type 1 Diabetes - Exogenous Insulin:
(a) Inhaled insulin
- Begins working within 12 to 15 minutes, peaks by 30 minutes, and is out of your system in 180 minutes.
- Types: Technosphere insulin-inhalation system (Afrezza)
- Not recommended for people with pulmonary disorders, contraindicated in smokers.
Pathophysiology - Type 2 Diabetes:
- Insulin is present, but = ?
Pancreas
Pathophysiology - Type 2 Diabetes:
- Insulin is present, but insulin not used by tissues (insulin resistance)
- Hyperglycemia
- Both hyperglycemia and hyperinsulinemia- beta cells gradually fail.
- Metabolic problems associated with fat and protein is not as severe.
- Undiagnosed for many years because onset/ progression is often gradual and signs are not noticed- aging population may not recognize increased thirst and urination abnormal.
- Diagnosed while getting treated for something else
Explain what’s happening in this picture = ?
Pancreas
(a) Normal:
- The pancreas produces a normal amount of insulin.
- Insulin receptors on cells function normally.
- Glucose enters cells easily and is used for energy.
- Blood sugar levels are maintained in a healthy range.
(b) Type 2 diabetes:
- The pancreas may produce less insulin, or the body may become resistant to the insulin it produces (insulin resistance).
- Insulin receptors on cells may become less sensitive to insulin.
- Glucose has difficulty entering cells and builds up in the bloodstream.
- Blood sugar levels become elevated, leading to the symptoms of diabetes.
(c) Notes:
- The main difference between normal and type 2 diabetes is how the body handles insulin and glucose.
- In normal physiology, insulin allows cells to take up glucose from the bloodstream, keeping blood sugar levels in check.
- In type 2 diabetes, this process is impaired, leading to high blood sugar and the associated health problems.
Type 2 Diabetes:
- Diagnostic Criteria = ?
- Laboratory Tests = ?
Pancreas
Type 2 Diabetes:
(a) Diagnostic Criteria:
- Random blood glucose levels equal to 200 mg/dl
- Fasting blood glucose levels
- 2 hour glucose tolerance test
- HbA1c- glycated hemoglobin
(b) Lab Test Values:
(b.1) A1C =
(b.2) FPG =
(b.3) OGTT =
Type 2 Diabetes:
- Lab Tests - Fasting glucose = ?
purple
Pancreas
Lab Tests - Fasting glucose:
Type 2 Diabetes:
- Lab Tests - HbA1c = ?
purple
Pancreas
Lab Tests:
Type 2 Diabetes:
- Lab Tests - OGTT = ?
purple
Pancreas
Lab Tests - Oral glucose tolerance test (OGTT):
Diagnostic Criteria for Diabetes = ?
Pancreas
Diagnostic Criteria for Diabetes:
Type 2 Diabetes:
- Urine analysis, what is present = ?
Pancreas
(a) Normally, urine analysis
- Negative for glucose
- Negative for ketones
(b) In diabetes,
- Glucose present
- Ketones present
Presence of antibodies against islet cells
Complications of Long-term Diabetes = ?
Pancreas
Complications of Long-term Diabetes:
(a) DM and resulting impact of short term and long term blood glucose fluctuations, can lead to a variety of complications ranging from acute medical emergencies to disability and death.
(b) Leading cause:
- blindness
- chronic kidney disease
- lower extremity amputations
(c) Macrovascular (coronary artery, cerebral, vascular and peripheral vascular disease)
- Atherosclerosis: Lipid accumulation, thickening of vessel wall- decreased vessel lumen size, reduced blood flow- risk of MI, stroke, impaired wound healing, gangrene, limb amputation.
- Cardiovascular complications: Left ventricular dysfunction, left ventricular hypertrophy.
- Microvascular (neuropathies, nephropathies, retinopathies)
(d) Kidney:
- Low blood flow - release of renin - angiotensin - angiotensin 1- angiotensin 2- increase blood pressure.
- End stage renal disease: kidney failure requiring transplant and dialysis
- Retinopathy: retinal ischemia, tissue death.
- In US, diabetes is leading cause of vision loss, chronic kidney disease.
- Foot ulcers
- Susceptible to infections
Treatments of Type 2 Diabetes = ?
Treatment of Type 2 Diabetes:
- Medications
- Diet
- Exercise
Pictures:
- Sedentary Control
- Sedentary Diabetic
- Exercise Control
- Exercise Diabetic
Just flip to see
Pictures:
- Sedentary Control
- Sedentary Diabetic
- Exercise Control
- Exercise Diabetic
Summary - Types of Diabetes:
(a) Type-1:
- Onset = ?
- Cause = ?
- Treatment = ?
(b) Type-2:
- Onset = ?
- Cause = ?
- Treatment = ?
(c) Gestantional:
- Onset = ?
- Cause = ?
- Treatment = ?
(1) Type-1:
- Onset:
- Puberty or childhood (peak at 10-14 years); although increasing in adulthood.
- Cause:
- Insulin deficit
- Treatment:
- Insulin replacement balanced with exercise and diet.
(2) Type-2:
- Onset:
- Adult years (peak at age 45 years); although increasing in those under age 45 years.
- Cause:
- Insulin resistance or impaired ability of the tissues to use insulin; insufficient insulin in relation to the needs of the body.
- Treatment:
- Diet
- Exercise
- Oral lycemic agents
- Possibly insulin
(3) Gestantional:
- Onset:
- Pregnancy (peak at 5th or 6th month gestation).
- Cause:
- Insulin resistance during pregnancy as a result of too much hormone production in the body (for the placenta); inability to make the additional insulin that is needed during pregnancy.
- Treatment:
- Diet
- Exercise
- Insulin (sometimes)
- Delivery of baby
