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Insulin Secretion Quizlet

Insulin Secretion And Action

Insulin Secretion And Action

Maintains glucose despite wide fluctuation in consumption, utilisation and production in healthy humans NO - it stores it in signifcant amounts, metabolises substrates other than glucose, extracts enough glucose from ECF as low conc because entry isn't facilitated by Insulin What is used to generate energy during fasting? Metabolic demand is met by fatty acid oxidation What is udes to generate energy in a Prandial state? Regulate insulin to promote glucose uptake after meals Regulate glucose output from liver during fasting What are the 5 cell types found in the Pancreas and what do they produce? PP cells - produce pancreatic polypeptide Initially synthesised as preproinsulin - 110 amino acids from the beta cells The processed in pro insuil - 86 amino acids Proinsulin --> Insulin - 21+30 amino acids, 35 Amino acids - C peptide by endopeptidases in the golgi Endopeptidases cleave the C peptide from insulin --> break bonds between lysin 64 and arginine 65 What is the difference in stored and active insulin? Glucose enters cells via GLUT 1 - glucokinase is the sensor for insulin secretion when glucose >5mmol/l Glucose --> Glucolysis --> Increase ATP/ADP ration --> Closes K+ channels --> increases membrane potential -->opens calcium ion channels --> Insulin secretion What else raises intracellular ATP/ADP ration? Catabolism of amino acids such as arginine and leucine Activates G protein coupled receptor GLP-1R which activates adenyl cclase ---> increases intra cellular cAMP and PKa pathway --> increased Insulin secretion How do phosphorylated inositol compounds cause insulin secretion? Phospholipase C cleaves phosphatidlinositol4,5- bisphospathe into inosito1,4, 5 triphosphate and diacylglycerol. 1,4,5-triphosphate binds to a receptor in the plasma membrane --> calcium ion Continue reading >>

Insulin & Glucagon

Insulin & Glucagon

Sort What biological actions INCREASE due to glucagon? INCREASE IN: - Glycogenolysis - Gluconeogensis* - Fatty acid oxidation - Ketogenesis - uptake of AA (*Glucagon STIMULATES gluconeogenesis by increase gene expression of PEPCK. Does so by binding to CREB-P-a leucine zipper binding domain) Continue reading >>

Insulin Secretion And Action

Insulin Secretion And Action

In healthy human what are the blood glucose levels normally Why is the brain highly dependent on extracellular glucose concentration Metabolise other substrates other than glucose Extract enough glucose from extracellular fluid at low concentrations because entry is not facilitated by insulin It is made in pancreatic beta cells in the islet of langerhans Form of 2 chains joined by disulphide bonds. Insulin is initially synthesised as preproinsulin in pancreatic beta cells. Afterwards in the endoplasmic reticulum it is processed to produce pro-insulin Proinsulin is matured in the Golgi apparatus through the action of cellular enteropeptidases within the Golgi apparatus. Enteropeptidases cleave off C peptide from insulin by breaking the bonds between lysine 64 and arginine 65 and between arginine 31 and 32 It is produced and stored as a hexamer, while the active form is the monomer. The hexamer is inactive with more long term stability and acts to keep the highly reactive insulin protected. The insulin is stored in the vesicles ready for release Insulin secretion is triggered by increase in cytoplasmic calcium concentration. This is a result in the opening of voltage gated calcium channels in the plasma membrane. Opening of these channels is controlled by membrane potential which is determined by ATP sensitive potassium channels Glucose enters the beta cells through the glucose transporter GLUT-2. Glucokinase converts glucose to glucose-6-phosphate. Glucose undergoes glycolysis where lots of ATP is made. This leads to a rise in ATP:ADP ratio in the cell. Normally at low levels of glucose the ATP sensitive potassium channels are open allowing the efflux of potassium. So resting membrane potential is hyperpolarised at -70mV. The increased ATP:ADP ratio causes the ATP sensi Continue reading >>

Insulin Secretion And Replacement

Insulin Secretion And Replacement

T/F? insulin resistance alone is enough to cause hyperglycemia/DM2 False - DM2 requires both insulin resistance and progressive destruction of beta cells (decreasing production of insulin) order of insulin biosynthesis in pancreatic beta cells preproinsulin --> proinsulin --> insulin + C-peptide what activates beta cells to secrete insulin? glucose - it enters beta cell, makes ATP, closes K channel, causes influx of Ca, secretory granules with insulin, proinsulin and C-peptide are released this hormone is co-released from beta cells with insulin. slows the rate of gastric emptying --> controls how much glucose is absorbed at a time so blood glucose level is maintained what are two incretin hormones that can activate beta cells to secrete insulin? glucose dependent insulinotropic hormone (GIP) incretins increase insulin levels more when glucose is administered orally rather than through IV when glucose is given IV, two phases of insulin release can be seen. first phase - release of beta cell secretory granules closest to the beta cell membrane what are MODY mutations and how do they cause hyperglycemia? MODY - maturity onset-diabetes of the young Continue reading >>

1) Insulin Secretion

1) Insulin Secretion

Between meals, pancreatic beta cells produce and store insulin in intracellular vesicles called insulin granules. Insulin granules are membrane bound vesicles in which beta cells store insulin. Found in pancreatic beta cells. The hormone insulin is composed of two polypeptide chains: chain A and chain B. They are connected by two disulfide bonds. Both chains come from the same precursor protein: preproinsulin. The posttranslational processing and folding for preproinsulin into mature active insulin involves the formation of disulfide bonds and its cleavage (cleavage of signal sequence and chain C). => preproinsulin lacks disulfide bonds and cleavage => proinsulin has disulfide bonds but lacks cleavage => insulin has disulfide bonds and is product of cleavage After a meal, glucose concentration in the blood increases. Beta cells in the pancreas senses this increase in blood glucose levels and releases insulin into the blood stream. Glucose cannot penetrate the cell membrane. It needs a transporter protein, GLUT4. Insulin's job is to signal to target cells that the blood glucose levels are high and that now is a good time to deploy GLUT4 transporter to bring glucose into the cells. Thus, the function of insulin is to promote the uptake of glucose by muscle cells that use it for energy and by fat cells that store it as triglycerides, or fats, and by liver cells. It does this by upregulating GLUT4 in muscle, fat, and liver cells. How is stored insulin released from the pancreatic beta cells into the blood stream? **Insulin secretion is regulated by glucose 1) when glucose levels are high, GLUT2 transporter allows glucose to enter beta cells. ***In pancreatic beta cells, it is GLUT2 and they are always present. In muscle and fat cells, it is GLUT4. 2) The increased concentr Continue reading >>

Beta Cell Biology And Insulin Secretion

Beta Cell Biology And Insulin Secretion

Where are insulin and glucagon islet cells located? Insulin expressing B cells in core of islet What are the paracrine interactions of the three hormones? Insulin - inhibits glucagon and SST release How does insulin biosynthesis in B cells? Nucleus - transcription of insulin gene - preproinsulin mRNA Preproinsulin is rapidly cleaved to proinsulin GA - proinsulin packaged into secretory granules Proinsulin is an insulin precursor peptide, contains a connecting peptide as well as the A- and B- chains of mature insulin. How does the cleavage of the C-peptide from proinsulin happen? Peptidases in the secretory granules cleave proinsulin to produce active insulin and free C-peptide Insulin A-chain has 21AA's B-chain has 30 AA's Chains are connected by two disulphide bonds Insulin has a highly conserved between species How is insulin synthesized in secretory granules? Proinsulin converted to insulin and C peptide Mature insulin has low solubility and forms crystals with Zn2+ Basal insulin secretion about -0.4ng/ml (70pM) Rises 5-10 fold when glucose levels increase Secreted insulin circulates in the blood as a monomer Circulating insulin has a half-life of about 5 mins What are the other regulators of insulin secretion? Hormones called incretins released from the GI tract in response to food intake potentiate glucose-stimulated secretion Glucose-dependent insulinotropic polypeptide (GIP) Continue reading >>

Insulin Secretion And Replacement

Insulin Secretion And Replacement

small intestine post prandial (food ingestion) insulin secretion this is why insulin response is greater in oral dose than IV dose Pancreatic polypeptide (PP) producing cells transcribed in nucleus to make preproinsulin preproinsulin transported to secretory granule where it is cleaved into insulin and C-protein DPP IV inhibitors used for T2DM medications 1st phase is release of insulin from secretory granules 2nd phase is newly made insulin which continues being made as long as IV glucose is administered lean body with diabetes at young age, no ketogenesis 6 MODY types, MODY 2 is glucokinase defect, MODY 3 is defect insulin transcription. They are most common recurrent severe beta cell dysfunction and ketogenesis during first presentation due to toxic effects of glucose on b-cell insulin treatments can be discontinued after a while insulin resistant with defective insulin secretion impaired insulin secretion, loss of early insulin response, altered pro-insulin to insulin ratios, altered insulin pulse, defective glucose recognition post-prandial insulin secretion is delayed, loss of early insulin response delayed response of insulin to glucose but other secretagogues lead to normal insulin release incomplete cleavage of pro-insulin to insulin, and residual pro-insulin detected in serum in T2DM, secretion is out of phase and this downregulates insulin receptors Mechanisms of beta cell dysfunction: amylin decrease in beta cell mass in T2DM, with deposition of amylin (marker of apoptosis of B-cells) less amylin secreted, amylin inhibits glucagon high glucose and fats are toxic to pancreatic beta cells this is why fatty and sugary diets can lead to diabetes basal insulin dose to keep insulin at constant physiological levels can use insulin pump to constantly fuse basal dos Continue reading >>

Insulin And Glucagon

Insulin And Glucagon

Sort symptoms of hypoglycemia adrenergic symptoms: - from a sudden drop in glucose - anxiety, palpitations, tremor, sweating - from epinephrine release regulated by hypothalamus, and adrenals in response to hypoglycemia neuroglycopenia - gradual decrease - not sudden - not enough to trigger adrenergic response <40 mg/dl - if severe and prolonged causes impaired brain function headache, confusion, seizures, coma, death hypoglycemia and alcohol intoxication - massive incr in cytosolic NADH = pyruvate -> lactate = lactic acidosis = OAA -> malate - these rxns decrease gluconeogenesis and can cause hypoglycemia in patients without glycogen - decreased OAA and increased acetyl CoA = alcoholic ketoacidosis - alcohol = increase TAG because decrease FFA ox = fatty liver - if continued = alcoholic hepatitis or alcoholic cirrhosis Continue reading >>

Interaction Of Insulin And Glucagon /control Of Insulin Secretion

Interaction Of Insulin And Glucagon /control Of Insulin Secretion

what do insulin and glucagon work together to achieve ? maintain constant blood glucose concentration antagonistic hormones -work against each other what is the system of maintaining blood glucose concentration? why is the system of maintaining blood glucose concentrations self regulating ? as level of glucose in blood determines quantity of insulin and glucagon released what doe blood glucose concentration do instead of being constant? what is the fluctuation of blood glucose concentrations around a set point a result of ? why in times of stress is adrenaline released by body ? to raise blood glucose concentration to allow more respiration to occur what happens when blood glucose concentration rises above set level? detected by beta cells in islets of langerhans and insulin is released what occurs at beta cells during normal blood glucose concentrations ? -potassium channels in plasma membrane of beta cells are open what happens at beta cells when blood glucose concentration rises ? glucose enters cell by glucose transporter what happens to glucose when it enters beta cells ? glucose metabolised inside mitochondria , resulting in production of ATP what happens to ATP produced in beta cell by metabolisation of glucose ? -ATP binds to potassium channels , causing them to close what are the potassium channels that ATP binds to known as ? Continue reading >>

Insulin And Glucagon Secretion

Insulin And Glucagon Secretion

islets of langerhans, secretin insulin and glucagon, somatostatin, and pancreatic polypeptide secretes digestive enzymes and bicarbonate into duodenum body's energy reserves: short term supply insulin actions promoting energy reserve preservation antilipolytic and antiketogenic, antigluconeogenic glycogenic and lipogenic, amino acid uptake and protein production Na-K ATPase, drives cellular K+ influx and Na+ efflux in patients with renal failure: can rapidly and temporarily relieve hyperkalemia shift of K+ out of cells with concomitant shift of H+ into cells--associated with normal anion gap (hyperchloremic) high anion gap acute metabolic acidosis is not associated with shift of K+ out of cells and shift of H+ into cells Rough ER: leader sequence directs entry to ER remainder forms B,C, and A peptide domains N-terminal cleavage removes 24 aa leader sequence folding forms S-S bonds that stabilize tertiary structure central C peptide region cleavage from proinsulin begins in Golgi maturate and keep converting proinsulin to insulin, driving crystal formation two monomers dimerize and associate with zinc and associate with each other, 2 Zn hexamers for compact intragranular storage alkalinization destabilizes crystalline form and hexamers degrade into dimers an monomers supplies 30% of liver's blood, oxygen-rich and nutrient-poor supplies 70% of liver's blood, oxygen-poor but nutrient rich promotes proper folding within ER to promote/stabilize disulfide bond formation between A and B peptides may play role in minimizing neurological and microvascular diabetes-related damage most numerous cells in islets of langerhans predominantly central localization within islets proinsulin--5% level of insulin, weak insulin action amylin--causes plaque formation may cause diabetes ACh s Continue reading >>

Endocrine Pancreas: Insulin And Glucagon

Endocrine Pancreas: Insulin And Glucagon

Sort 5 steps of insulin release (explain/draw) 1. GLUT2 transporters bring glucose inside B cells. glucose floats down concentration gradient. passive facilitated diffusion. 2. glucose metabolized to produce ATP 3. when ATP is present it binds to K channels, and closes them. this results in more K staying inside cell. K is positive, so the inside of cell gets more positive, causing B cell to depolarize 4. calcium channels respond to depolarization. when B cell is at resting potential, the channel is closed. when it depolarizes in response to glucose, the channel opens---calcium influx. 5. calcium influx triggers exocytosis of vesicles with insulin inside GPCR signaling cascade 1. GPCR binds to a signal; G-protein binds to GTP and is activated, initiating a signaling cascade. 2. G-protein activates adenylyl cyclase (an amplifier enzyme that takes a signal and amplifies it in the cell) 3. this changes ATP to cAMP 4. G-protein can either be stimulatory or inhibitoyr. Continue reading >>

Insulin, Pancreas

Insulin, Pancreas

Sort Explain the steps of regulation of insulin 1. Glucose enters the beta cells via GLUT2 receptor 2. Cellular respiration > ATP production 3. ATP sensitive K+ channel pump inhibits K+ from leaving the cell and the cell becomes depolarized 4. Voltage gated Ca2+ channels open due to depolarization and Ca2+ enters the cell 5. Ca2+ stimulates exocytosis of vesicles containing insulin 6. Insulin enters the blood stream via that exocytosis How are target cells activated by insulin? tyrosine kinase Insulin receptor is activated by insulin and autophosphorylates when bound. A primary effect:Translocation of glucose transporter 4 (GLUT4) to the target cell membrane. GLUT4 is found in striated muscle & adipose GLUTs transport glucose into cells via facilitated diffusion What are the major effects of glucagon on target cells? Glucose utilized by muscle cells Liver cells release glucose into bloodstream Through the breakdown of triglycerides By conversion of amino acids from bloodstream Glucose is released into bloodstream What are some treatments for DM-1? Which insulins are short acting and which are long? Humulin™ (insulin isophane & insulin regular) -short Humalog™ (lispro) -short Lantus™ (glargine) -long Levemir™ (detemir) -long Continue reading >>

Endocrine Pancreas- Glucagon & Insulin

Endocrine Pancreas- Glucagon & Insulin

Sort Describe what happens in diabetic ketoacidosis No insulin = Not enough receptors Cells can't take in glucose Starved for fuel Lipolysis releases FFAs FFAs make Ketones Ketones are acid= Metabolic Acidosis Hyperventilation to compensate Acidosis causes hyperkalemia No insulin: K+ can't get into cell High glucose spills into urine causes volume loss DKA: Acid and K+ effect - cells starved for glucose -lypolysis to increase free fatty acids for energy - FFAS lead to lipid trash called ketones - ketones are acid - transcellular acid shift -blood potassium up - potassium spills into urine - blood level up of potassium; body level down Dipeptidyl Dipeptidase 4 inhibitors Sitagliptin Saxagliptin Linagliptin - Prevent breakdown of Glucose-dependent insulintropic peptide and Glucagon like peptide - Increase insulin release - Decrease Glucagon - Slow stomach motility Describe glucagon - produced by alpha cells (10-20% of islet cells) - liver hormone - raises glucose - raises FFAs - uses amino acids to make glucose instead of protein - increases gluconeogenesis - breaks down glycogen (glycogenolysis) - inhibits glycogen formation - increases lipolysis - decreases lipogenesis - increases FFAs - increases ketones Continue reading >>

Insulin Flashcards | Quizlet

Insulin Flashcards | Quizlet

once nutrients have been absorbed, you shift into the "what or what" state? Concentrations of what 2 things fall in the plasma? You shift into a state of BLANK preventing concentrations of what molecules from falling to far? This keeps what from going too low or high? once nutrients have been absorbed, you shift into the "postabsorptive" or "fasted" state. Concentrations of glucose and amino acids fall in the plasma. You shift into a state of Catabolism preventing concentrations of small molecules from falling to far. This keeps plasma glucose from going too low. glucose concentrations should vary from (#s) glucose concentrations should vary from 80-120 mg/dL plasma. limits fluctuations so glucose doesnt go too high or too low This switch between anabolism and catabolism is mediated by hormones secreted by what place in the body, what 2 things are secreted? This switch between anabolism and catabolism is mediated by hormones secreted by the pancreas, insulin and glucagon (stimulates an increase in blood sugar levels, thus opposing the action of insulin). endocrine secretes hormones directly into blood insulin is BLANK. causes what molecule to go to what 3 things? anabolic (causes glucose -> glycogen & amino acid -> protein) beta cells interact with what to secrete what? beta cells interact with glucose to secrete insulin hormones are secreted by "what" of which cells in where? hormones are secreted by "islets" (endocrine) of endocrine cells in the pancreas soon after eating, blood glucose decreases or increases?, acts directly on which cells and causes what secretion? soon after eathing, blood glucose increases, acts directly on beta cells and causes insulin secretion binding activates what? The receptor does what to itself? and also does this to various what? binding Continue reading >>

Diabetes

Diabetes

Sort Glucose Metabolism: -Most cells, including ____ and the ____ rely on glucose as a fuel source. -Because the brain cannot synthesize or store more than a few minutes' supply of glucose, normal cerebral function requires _____. -Severe or prolonged ____ can cause brain death and dysfunction. This the coma associated with diabetes. -brain; nervous system -a continuous supply from the circulation -hypoglycemia -About 2/3 of the glucose that is ingested with a meal is removed from the blood and stored in the ___ as ____. -Blood glucose levels reflect the difference between ___and _____. -Body tissues obtain glucose from the ____. -In nondiabetic patients, fasting blood glucose is tightly regulated between _____mg/dL. After a meal, the blood glucose levels ___ and ___ is secreted in response. -liver; glycogen -the amount of glucose released into the blood stream by the liver and the amount of glucose taken up by the cell for energy -blood -70-100; rise; insulin -Glucose is ingested through the ____ -Between meals, the ___ releases glucose as a means of maintaining blood glucose within normal range -Glucose is an optimal fuel for tissues such as ____, ____, and ____. -Glucose that is not needed for energy is stored as ____ or converted to ____. -When glucose levels rise, _______. When blood glucose levels fall, _____. -diet -liver -muscles; adipose tissue; and the liver -glycogen; fat -glucose is removed from the blood and converted to glycogen; the liver glycogen stores are broken down and released into the circulation. Roles of the liver: -In addition to mobilizing its glycogen stores, the liver ____ from noncarbohydrate sources such as amino acids, lactic acid, and the glycerol part of triglycerides. -When blood glucose levels fall below normal, glycogen is broken down Continue reading >>

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