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40 Cards in this Set
- Front
- Back
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What do the alpha cells of the pancease release and what is its function?
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Glucagon; increase blood glucose levels
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What do the beta cells of the pancrease release and what is its funtion?
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Insulin; lower blood glucose levels
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What do the gamma cells of the pancrease release and what is its function?
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somatostatin; inhibits secretion of insulin and glucagon
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What happens when there is a high blood glucose level?
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High blood glucose leads glucose uptake into the pacrease beta cells where it is phosphorylated by hexokinase and catabolism of glucose elevates beta cell ATP levels.
Elevated ATP levels clost ATP-gated K+ channels resulting in membrane depolarization and Ca++ influx This is followed by insulin exocytosis |
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What are insulins effects on the liver?
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inhibits glycogenolysis
inhibits gluconeogenesis inhibits ketogenesis promotes glycogenesis promotes triglycerideogenesis and LDL formation |
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What is insulins affect on skeletal muscle?
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PROMOTES PROTEIN SYNTHESIS by increasing aa transport and ribosomal protein synthesis
INCREASES GLYCOGENESIS by increasing myocyte glucose uptake and |
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What is insulins affect on adipose tissue?
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INCREASED TRIGLYCERIDE STORAGE
lipoprotein lipase is induced and activated by insulin to mobilize TGs from lipoproteins which are in the blood inracellular lipase is inhibited NET EFFECT IS TO INCREASE FAT STORAGE |
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Where do diabetis have the most trouble uptaking glucose and what is the effect.
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Diabetics can not uptake glucose primarily in muscle and adipose tissue leading to a state of cellular starvation due to low ATP
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What does the liver to when it is signaled that the body is low in ATP?
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It increases hepatic glycogenolysis and subsequently increases the amount of glucose entering the blood.
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What is the result of increased liver glycogenolysis?
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The diabetic patient experiences hypreglycemia and this elevates blood volume, urine output, thirst, muscle weakness, and weight loss may follow
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What happens with continued shortage of glucose within cells? What does ammonia have to do with anything?
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Continuous shortage of glucose within cells increases gluconeogenesis by using proteins
converting amino acids to glucose causes the release of amonia into urea which can lead to Azoturia. |
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What is Azoturia?
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a condition that damages muscles
Equine Exertional Rhabdomyolyosis |
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How does the diabetic patient experience hyperlipidemia?
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This causes the adipose tissue to increase triglyceride levels and LDL concentration to transport the TG
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What happens when Ketogenesis is a result of diabetes?
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This is the accelerated catabolism of TGs via beta oxidation and it leads to the formation of ketone bodies
this results in ketonemia and ketouria which leads to diuresis and dehydration |
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The formation of ______ is favored when there is an elevated intracellular glucose concentration.
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sorbitol
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What happens if there is an elevated sorbitol concentration?
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inreased sorbitol osmotically blocks cell function and leads to cell rupture
this can cause cataracts, retinopathy, nephropathy, or peripheral lesions |
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What are the characteristics of Type I diabetes?
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usually occurs during childhood or puberty
usually occurs due to fequent undernourishment weak genetic predisposition beta cells destroyed eliminating production of insulin prone to ketoacidosis and other manifestations of sever diabetes |
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What are the characteristics of Type II diabetes?
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occurs frequently to people over 35
obesity is usually present strong genetic factor results in beta cells inability to produce appropriate amount of insulin; insulin resistance or other unknown defects ketoacidosis rare; insulin therapy not always required |
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How many amino acids does proinsulin have total, on A chain, on B chain?
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86 AA total
21 AA on A chain 30 AA on B chain |
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what animals have the most immunogenic potency?
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beef > pork > human
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How are human insulins mass produced?
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in E. coli or yeast by inserting human proinsulin gene and treating the extracted proinsulin
beef and pork insulin production has been eleminated due to more efficient and fiscally responsible ways to produce human insulin |
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What are the names of the following forms of insulin:
Ultra-short acting Short-acting intermediate-acting long-acting |
ultra short is lispro, aspart
short acting is crystalline zinc intermediate acting is lente and isophane long acting is ultralente |
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What does zinc do to insulin preperations?
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increases shelf life (stability)
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What is Isophane a combination of?
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insulin and protamine and neutral pH so nither is uncomplexed ("isophane")
the protamine is a mixture of Arg-rich basic peptides isolated from rainbow trout sperm |
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How does Isophane (lente) produce an extended duration?
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never IV
proteolytic enzymes degrade the protamine to permit insulin absorbtion. This breakdown of protamine forms an isophane |
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What makes Ultalente versions unique?
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Large crystals of insulin with high zinc content
relatively insoluble |
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What are is the % of lente formulation breakdown?
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stable mixture
70% ultralente 30% semilente (rapid acting) this provides rapid absorbtion along with sustained release |
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What is unique about lispro (Humalog) insulin?
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ultrashort acting
recombinant human insulin analog the aa at positions 28 and 29 on the B chain are reversed (Pro-Lys switched to Lys-Pro) |
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Why is the 28th and 29th amino acid in lispro reversed?
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cause it blocks aggregation and improves solubility
doesnt change binding; half life; or immunogenicity |
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What is unique about Glargine insulin? (Lantus)
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Ultra long acting
recombinant glargine is formed when Asn is substituted by Gly at position 21 on A chain and Arg-Arg remains at positions 31 and 32 of B chain carboxyl terminal |
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How does Glargine Insulin work? (Lantus)
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it is soluble at pH4 and forms precipitates after SC (ph 7) and this forms a microprecipitate depot
insulin slowly dissolves from the dept providing peakless basal insulin replacement (broad plasma concentration plateau) |
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What makes the new long acting insulin Detemir (Levemir - Novo Nordisk) different?
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Elimination of threonine and position 30 and an addition of a 14-carbon fatty acid chain at pos B29
The fatty acid side chain binds albumin increasing duration of action |
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What is Amylin?
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a hormone secreted with insulin from B-cells after meals; single chain peptide w 37 aa
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What is the mechanism of action for amylin?
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Binds to receptors in CNS
Decreases glucagon release and lowers glucose levels Slows gastric emptying can not give native amylin since it will coil and aggregate |
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What is symlin?
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amylin analogue with proline mutants at positions 25, 28, and 29 to help solubility and inhibit aggregation
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What is GLP-1?
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glucagon like peptide 1
hormone secreted by endocrin L cells of small intestine its two peptides 30 and 31 aa in lenth |
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What is the mechanism of action for GLP-1?
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Stimulates release of insulin from B-cells
Inhibits release of glucagon slows gastric emptying by binding to GLP-1 receptors released when food in stomach |
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What is the half life of GLP-1 and how is it metabolized?
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half life is 90 seconds
metabolized by dipeptidyl peptidase IV (DPP-IV) |
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What is Exenatide (Byetta)?
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synthetic GLP-1
half life 2-4 hours |
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What is sitagliptin (Januvia)?
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DPP-IV inhibitor
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