Endocrine Pancreas Flashcards
Who are the main players in control of plasma glucose? What are some other players?
Insulin (storage) and Glucagon (mobilization)
Also epinephrine (inhibits insulin secretion and stimulates glycogenolysis in peripheral cells and gluconeogenesis in hepatic cells). Also Cortisol and Growth Hormone (reduce insulin sensitivity at receptors and stim glycogenolysis and gluconeogenesis). ALos Thyroxine (Increase glucose absorption w/o insulin and enhance insulin breakdown)
Four groups of cells in Islets of Langerghans. What are they, and what do they make?
Alpha cells - Glucagon (and GLP-1 and 2) (20% total cells)
Beta cells - Insulin (and amylin, GABA, PTHrP) (70%)
Delta cells - Somatostatin
F cells - Pancreatic PolyPeptide (PP) (Very few)
Describe insulin synthesis and release.
Synth in RER and Golgi. Preproinsulin to proinsulin, which is complexed with zinc and conversion enzymes in secretory vesicles in beta cells. Then, cleaved into insulin and Peptide C, and released.
How long does insulin stay in the plasma? What is breakdown enzyme.
Half life of five minutes. Breakdown enzyme is insulinase, called metalloproteinase.
How does presence of glucose in blood affect synthesis and release of insulin from beta cells of pancreas?
Synthesis is STIMULATED when glucose enters the cells, because causes a membrane depolarization by shutting off potassium channels and opening calcium channels and excretes the vesicles, which causes the metabolism of the proinsulin to insulin.
Release is both direct (above) and “permissive,” as other stimulants can have similar effect on membrane.
Permissive release of Insulin. Other things affect than just glucose. Tell me some of the things that STIMULATE release of insulin from beta cells.
Nutrients: (glucose), fatty acids and ketone bodies, amino acids
Hormones: Glucagon (when reaches a certain level), Secretin, Incretins
Parasympathetic NS (muscarinic agonists): excites insulin release
Permissive release of Insulin. Other things affect than just glucose. Tell me some of the things that INHIBIT release of insulin from beta cells.
Sympathetic NS (NE at alpha2 receptors)
Somatostatin (from delta cells)
Insulin (negative feedback - have enough in the system)
Amylin (from beta cells)
Epinephrine can both excite and inhibit pancreatic insulin release at different cells (excites beta2 and inhibits alpha2)
What is the acute cellular response to insulin docking in receptor?
Phosphorylation of glucose transport protein (GLUT4) to the membrane to allow glucose a channel through to cytoplasm.
How does the body “time” intracellular actions of making new glucose vs. creating glycogen to store excess glucose?
Inhibition (stopping) of gluconeogenesis happens at a lower insulin level than glycogenesis begins. We want to stop making new glucose before we start storing it.
Insulin effects on metabolism of carbohydrates in LIVER.
Decrease gluconeogenesis.
Increase glycogenesis.
Decrease glycogenolysis.
Insulin effects on metabolism of carbohydrates in ADIPOCYTES.
DECREASE glucose uptake!
INCREASE glycerol synthesis.
Insulin effects on metabolism of carbohydrates in MUSCLE.
Increase glucose uptake.
Decrease Glycolysis.
Increase Glycogenesis.
Insulin effects on metabolism of LIPIDS in LIVER.
Increase lipogenesis.
Decrease lipolysis.
Insulin effects on metabolism of LIPIDS in Adipocytes.
INCREASE Free Fatty Acid synthesis.
INCREASE Triglyceride synthesis (FFA + Glycerol - reason for weird pattern with insulin effects on carbs in fat tissue)
Decrease Lipolysis.
Insulin effects on metabolism of PROTEIN in Liver.
Decrease protein catabolism.
Insulin effects on metabolism of PROTEINS in MUSCLE.
Increase amino acid uptake.
Increase protein synthesis.
Glucagon Synthesis. Where does it happen?
Alpha cells of pancreas.
L cells of Lower GI tract.
Brain.
Mechanism of glucagon synthesis in different areas of production.
Alpha cells - glucagon and some glucagon fragments.
L cells of Lower GI - Glicentin, Incretins (GIP1 and GIP2) (gut hormones, upregulated during fasting), oxyntomodulin (acts like glucagon)
Stimulators of Glucagon synthesis
Hypoglycemia (need free sugar in blood!) Glucogenic AAs (ala, ser, gly, cys, thr) CCK and gastrin Cortisol Sympathetic NS and Epinephrine Beta-agonists (upreguate Insulin production) Parasympathetic NS via ACh
Inhibitors of Glucagon Synthesis
Glucose Insulin Somatostatin (D cells of pancreas) Secretin (promotes insulin release) FFAs and ketones alpha-agonists? GABA
In general, when glucagon is in the blood, what is the body trying to do?
Trying to MOBILIZE ENERGY, so causing glycogen breakdown and gluconeogensis, and adipose tissue break down, and some ketoacids.
How does adipose tissue act as an endocrine organ?
Fat cells synthesize and release hormones called adipokines. Many act against insulin, including RESISTIN, IL-6, free fatty acids, AND TNFalpha. The more fat tissue there is, the more of these hormones there are, and the more insulin resistance builds up.
LEPTIN, on the other hand, is a signal from fatty tissue that aid’s insulin, and acts as a SATIETY hormone.
Talk about Leptin. Where is it made? What does it do?
Made in fatty tissue, amounts depending on how much fat in the diet.
Acts in brain to lower appetite.
Can have resistance build up if there is TOO MUCH Leptin, and then leptin will not have affect, and organism will get fat and lazy, oopsy-daisy.
Difference between Type I and Type II diabetes.
Type I: Something wrong with insulin production or release or control. Often autoimmune action on beta cells of pancreas.
Type II: Decreased action of insulin receptors due to chronic high levels of blood sugar and high levels of insulin, which ultimately causes the beta cells to poop out and secretion is impaired.
