CH 7 Endocrine Pancreas Flashcards
What does EXOcrine pancreas do?
secrete alkaline fluid rich with digestive enzymes into small intestine
What is the functional unit of ENDOcrine pancreas?
islets of Langerhans
What cell types are in the islets of Langerhans? What do they secrete?
beta (insulin), alpha (glucagon), delta (somatostatin), other (pancreatic polypeptide)
How do endocrine pancreas hormones reach circulation? What is the major target organ?
hepatic portal vein. liver
What are the neurotransmitters of parasympathetic stimulation?
acetylcholine, vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, & gastrin-releasing peptide
How does the Vagus N. (parasympathetics) effect the pancreas?
stimulate secretion of insulin, glucagon, somatostatin, and pancreatic polypeptide
What are the neurotransmitters of sympathetic stimulation?
norepinephrine, galanin, neuropeptide Y
How does Sympathetic Nerve Stimulation effect the pancreas?
inhibits basal and glucose-stimulated insulin secretion & somatostatin release; stimulates glucagon & pancreatic polypeptide secretion
What type of regulation is Insulin under?
Pancreatic B-cells respond to plasma levels of energy substrates (glucose/amino acid), hormones (insulin, glucagon-like peptide I, somatostatin, epinephrine), & neurotransmitters (norepinephrine/acetylcholine)
Track how glucose stimulates insulin secretion.
Glucose is transported into pancreatic B-cell by GLUT2. Glucose is phosphorylated & undergoes oxidative phosphorylation to make ATP. When conc. of ATP is high, it causes ATP-sensitive K+ channels (sulfonylurea receptor) to close (K+ was going out to hyperpolarize cell). Cell becomes depolarized, and Voltage-dependent Ca++ channels open and Ca++ rushes in. Ca++ lead to fusion of insulin-containing secretory granules to fuse with plasma membrane and release insulin.
What receptor regulates ATP sensitive K+ Channels?
sulfonylurea (used in treatment of diabetes)
What is a major characteristic of glucose-stimulated insulin secretion?
it is biphasic; release throughout the day is pulsatile and rhythmic
What type of physiologic effect does insulin have on metabolism?
anabolic
What is the IRS-PI3K Pathway?
insulin receptor substrates-phosphatidylinositol 3-kinase pathway: mediates insulin’s metabolic effects (glucose transport, glycolysios, glycogen synthesis, regulation of protein synthesis)
What is the MAPK pathway?
mitogen-activated protein kinase pathway: mediates proliferative and differentiation effects of insulin
What protein does insulin stimulate in muscle and adipose tissue for glucose uptake?
GLUT 4 (recall: GLUT 2 is in pancreas as glucose sensor). GLUT 4 is typically held within cell until stimulation by insulin translocates proteins to membrane
What is GLP 1? Where is it produced? When? What effects does it have?
product of proglucagon processing (aka Incretin); produced in intestine from proglucagon processing); occurs in response to a glucose load (e.g. after eating); amplifies insulin release from B-cells of pancreas
What are the two products of proglucagon processing?
glucagon (alpha cells of pancreas) & GLP1 (intestine)
How does somatostatin effect insulin & glucagon release?
inhibits both
What kind of meal stimulates glucagon release?
high in amino acid levels
How does epinephrine effect insulin and glucagon release?
inhibit insulin (alpha2-adrenergic receptors), stimulate glucagon (beta2-adrenergic receptors)
What stimulates release of somatostatin from delta-cells of pancreas?
high fat, high carbohydrate, high protein meals
What inhibits release of somatostatin from delta-cells of pancreas?
insulin
Where does pancreatic polypeptide come from? What role does it play?
endocrine type F cells of pancreas; inhibits pancreatic exocrine secretion (alkaline secretion), gallbladder contraction, modulation of gastric acid secretion, and gastrointestinal motility. Regulates feeding behavior (appetite suppression).
What is Amylin? What does it do? Why is it important?
peptide released with Insulin by pancreatic B-cells that suppresses glucagon secretion and gastric emptying. Deposition of amyloid in pancreas leads to B-cell destruction (seen in type II non-insulin-dependent diabetes). In type I diabetes, almost no amylin present with no secretion after meals. In type II diabetes, normal amyline levels, but no increase following meals)
How does an insulinoma present?
hypoglycemia, confusion, aggressiveness, palpitations, sweating, convulsions, unconsciousness. (observed before breakfast and after exercise)
How do glucagonomas present?
symptoms of diabetes, severe weight loss, anorexia
define polyuria
excess loss of water and sodium
define polydipsia
thirst via dehydration
define polyphagia
hunger
What is type 1 diabetes mellitus
insulin-dependent diabetes mellitus (Beta-cell destruction), less common aka “juvenile-onset diabetes”
adolescent presents with ketoacidosis. What is the likely diagnosis?
type 1 diabetes mellitus
What is type 2 diabetes mellitus
insulin-independent diabetes mellitus (loss of normal regulation of insulin secretion), decreased responsiveness of peripheral tissues to insulin & inadequate responsiveness of B-cells to glucose
What disease is often associated with type 2 diabetes mellitus? How does it present?
syndrome X aka “insulin-resistance syndrome”; hypertension, atherosclerosis, central obesity
How does diabetes progress?
Accumulation of glucose in blood (hyperglycemia) –> increased plasma osmolarity –> polyuria along with urinary loss of glucose –> polydipsia. Patient also experiences polyphagia –> lipolysis / proteolysis –> diabetic ketoacidosis
How does diabetes type 2 insulin secretion work?
patients secrete a regular amount of insulin during fasting and after a meal, not enough insulin is secreted and it is secreted in smaller, sluggish, and erratic pulses. this results in higher levels of fasting glucose after a meal.
What is the earliest sign of type 2 diabetes?
B-cell dysfunction: delay in acute insulin response to glucose –> hyperglycemia –> hyperinsulinemic response –> downregulation of insulin receptors (in response to sustained insulin) –> decreased tissue sensitivity to insulin
What level of fasting glucose must be hit for a diagnosis of diabetes?
126mg/dL
What level of random glucose must be met for a diagnosis of diabetes?
200 mg/dL in association with symptoms of diabetes (polyuria, polydipsia, polyphagia)
How does hypoglycemia present?
Excess Insulin –> hypoglycemia. Stress response to try to restore normal glucose levels. SNS –> catecholamines. HPA –> cortisol.
glucagon release (via cortisol to pancreas), GH release; tachycardia, palpitations, sweating, tremors, irritability, confusion, blurred vision, tiredness, headache, difficulty speaking, loss of consciousness or seizures if severe
What is Diabetic Ketoacidosis? What causes it?
Type I Diabetes - no insulin. hyperglycemia. Ketoacidosis is precipitated by stress (infection, hospitalization, trauma, surgery) - stress increases catecholamines (epi/norepi) + cortisol –> lipolysis and ketone bodies
What is a Hyperglycemia Hyperosmolar Coma?
type II Diabetes - lack of insulin. hyperglycemia –> hyperosmolar dehydration –> coma
