Term
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Definition
| Hyperglycemia; absent or inadequate insulin secretion |
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Term
Type 1 diabetes is best described as:
1. insulin-dependent
2. non-insulin-dependent |
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Definition
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Term
| Insulin is stimulated by... |
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Definition
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Term
| What are the 4 main actions of insulin? |
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Definition
1. Increase glucose uptake
2. Increase glycogen synthesis
3. Decrease glycogenolysis
4. Decrease gluconeogenesis |
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Term
| Insulin secretion normally results in (increased/decreased) blood glucose? |
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Definition
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Term
| Name 4 hormones that counter the effects of insulin |
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Definition
1. Glucagon
2. Adrenaline
3. Glucocorticoids
4. Growth hormone |
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Term
| What is the stimulus for the four main counter hormones of insulin (glucagon, adrenaline, glucocorticoids, and growth hormone), and what is their main effect? |
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Definition
| Hypoglycemia; increase blood glucose |
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Term
| What are the main actions of glucagon? |
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Definition
Increase glycogenolysis
Increase gluconeogenesis |
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Term
| What are the main actions of adrenaline? |
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Definition
Increase glycogenolysis
Decrease glucose uptake |
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Term
| What are the main actions of glucocorticoids? |
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Definition
Increase gluconeogenesis
Decrease glucose uptake |
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Term
| What are the main actions of growth hormone? |
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Definition
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Term
| Within the pancreas beta cells make up ____% of islet mass, and secrete what 3 products? |
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Definition
75%
Insulin, C-peptide, proinsulin, amylin |
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Term
| Within the pancreas alpha cells make up ____% of islet mass, and secrete what 2 products? |
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Definition
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Term
| During carbohydrate metabolism what effect does insulin have in: liver, fat, and muscle cells |
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Definition
Glucose uptake: increased in fat and muscle cells
Glycolysis: increased in liver and muscle cells
Glycogenesis: increased in liver and muscle cells
Glycerol synthesis: increased in fat cells
Gluconeogenesis: adjusts in liver cells |
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Term
| What effect does insulin have on muscle cells during fat metabolism? |
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Definition
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Term
| During fat metabolism what effect does insulin have in: liver, and fat cells? |
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Definition
Lipolysis: decreased in liver and fat cells
Lipogenesis: increased in liver cells
TG synthesis: increased in fat cells
Fatty acid synthesis: increased in fat cells |
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Term
| T/F During protein metabolism insulin has a great effect on fat cells. |
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Definition
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Term
| During protein metabolism what effect does insulin have in: liver, and muscle cells? |
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Definition
Protein breakdown is decreased in liver cells
Amino acid uptake, and protein synthesis are increased in muscle cells |
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Term
| Describe how the presence of insulin reverses catabolic metabolism in the liver |
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Definition
1. Stops glyconeogenesis
2. Stops AA/FA conversion to keto acids
3. Stops AA--> Glucose conversion |
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Term
| Describe how the presence of insulin induces anabolic metabolism in the liver |
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Definition
1. Induce glucose storage as glycogen
2. Increases TG synthesis |
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Term
| Describe insulin's effect on muscle cells? |
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Definition
1. Incr. protein synthesis
2. Incr. AA transport
3. Incr. glycogen synthesis
4. Incr. glucose transport
5. Inhibition of phosphorylase |
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Term
| Describe insulin's effect on fat cells? |
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Definition
1. Incr. TG storage
2. Lipoprotein lipase is induced
3. Esterification of FA
4. Intracellular lipase inhibited |
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Term
| Where do sulfonylureas work? |
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Definition
| B cells of pancreas islet |
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Term
| 4 ways to stimulate insulin release |
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Definition
1. Glucose, mannose
2. Leucine
3. Vagas stim.
4. Sulfonylureas |
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Term
| 4 drugs that inhibit insulin release |
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Definition
1. diazoxide
2. phenytoin
3. vinblastine
4. colchicine |
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Term
| Neural and humoral ways in which insulin release is inhibited |
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Definition
1. catecholamines
2. somatostatin
3. leptin |
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Term
| GLP-1, GIP, cholecystokinin, secretin, gastrin, and glucagon have what effect on insulin release? |
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Definition
| They act as glucose induced insulin release amplifiers |
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Term
| What amino acid (AA) amplifies glucose induced insulin release? |
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Definition
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Term
| In relation to glucose induced insulin release what effect does stimulating the beta adrenoceptors have? |
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Definition
| Amplifies glucose induced insulin release |
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Term
| 5 clinical uses of insulin |
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Definition
1. Type 1 DB
2. Type 2 DB
3. Gestational DB
4. Hyperglycemic emergency (ketoacidosis)
5. Hyperkalaemia |
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Term
| In NORMAL physiology which two organs remove insulation from circulation, and at what percentage? |
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Definition
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Term
| In insulin-treated DB which two organs remove insulation from circulation, and at what percentage? |
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Definition
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Term
| Half life of circulating insulin is? |
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Definition
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Term
| Describe the PK of insulin glargine (LANTUS) |
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Definition
1. No Conc. peak
2. Neutralized for SLOW release
3. SQ inj. once daily |
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Term
| Describe the MOA of sulfonylurea Type 2 DB agents. |
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Definition
Works @: Pancrease (Beta cells)
Via: ATP/K+ channels
Results in: membrane depol, Ca influx, insulin release |
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Term
| List 2 Meglitinides (NON-SU secretagogue) Type 2 DB agents, and their MOA. |
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Definition
1. repaglinide
2. nateglinide
MOA: SAME as SU agents |
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Term
| What class is metformin, and what is it's MOA. |
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Definition
Biguanide Type 2 DB agent
MOA:
1. Improves glucose ability to move into the cells
2. Decrease intestinal glucose absorption
3. Increase peripheral glucose utilization |
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Term
| a-glucosidase inhibitors are also known as ____________. |
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Definition
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Term
| List two a-glucosidase inhibitor agents, and describe their MOA. |
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Definition
1. acarbose
2. miglitol
MOA:
Works @ - small intestine inhibiting a-glucosidase enzymes(glucoamylasse, sucrase, maltase, dextranase)
Delays digestion/absorption of sucrose + complex carbs; decreasing postprandial hyperglycemia |
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Term
| The thiazolidinediones class of Type 2 DB agents are commonly known as _____________. List two example agents. |
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Definition
Insulin sensitizers.
1. pioglitazone
2. rosiglitazones |
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Term
| Describe the MOA of thiazolidinediones (AKA: insulin sensitizers, glitizones)in Type 2 DB |
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Definition
1. Ligand of PPARy
2. Reduces insulin resistance
3. Main site of action enhanced movement of glucose into fat tissue
4. Raises HDL levels by 10-20%! |
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Term
| List two dipeptidyl peptidase-IV inhibiting agents, and describe their MOA. |
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Definition
1. Sitagliptin (Januvia)
2. Saxagliptin (Onglyza)
MOA: Inhibits DPP-4 by 80% --> higher levels of GLP-1. |
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Term
| What class is the drug pramlintide (Symlin)? |
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Definition
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Term
| Limitations of sulfonylureas (glimepiride, glipizide, glyburide) |
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Definition
1. Less effective as # of function beta cells decrease.
2. Rarely work in FBG is >300mg/dL |
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Term
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Definition
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Term
| List 3 2nd generation sulfonylurea Type 2 DB agents. |
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Definition
1. glimepiride
2. glipizide
3. glyburide |
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Term
| Name some first generation SU agents |
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Definition
1. Tolbutamide
2, Toluzamide
3. Chlorproamide
4. SU |
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Term
| What is the shortest acting SU agent? |
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Definition
| Tolbutamide - useful in old peeps |
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Term
| Describe the effect of cytochrome p450 on SU agents |
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Definition
| CYP2C9 - renders SU agents inactive |
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Term
| Discuss the unique features of chlorpropamide... |
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Definition
1. 30% excreted unchanged in urine = problems for old peeps
2. Flushing after alcohol consumption (disulfiram-like effect) |
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Term
| Which SU agent is least likely to cause hypoglycemia? |
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Definition
| Glipizide (90% metabolized inactive by CYP2C9) |
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Term
| Which SU agents can be used once daily? |
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Definition
| 2nd generation (glyburide, glipizide, glimepiride) |
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Term
| What is the longest acting SU agent? |
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Definition
| Chlorpropamide (60hr duration) |
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Term
| An important consideration with 1rst gen SU agents is... |
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Definition
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Term
| List 4 unwanted effects of SU agents? |
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Definition
1. hypoglycemia
2. Weight gain
3. GI issues
4. CV death (1rst gen > glyburide) |
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Term
| List 3 SU agent drug interactions which are known to cause HYPOglycemia |
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Definition
1. Salicylates
2. Ethanol
3. Beta-blockers |
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Term
| List 5 SU agent drug interactions which are known to cause HYPERglycemia |
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Definition
1. Epi
2. glucocorticoids
3. CCBs
4. Clonidine
5. K+ depleting diuretics |
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Term
| Repaglinide (a non-SU insulin secretagogues) interacts with what CYP450? |
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Definition
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Term
| Describe the usefulness of Repaglinide (a non-SU insulin secretagogues). |
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Definition
1. Pts with SU allergy
2. Pts with renal impairment |
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Term
| What is the onset/duration of a non-SU insulin secretagogues? |
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Definition
Onset: 30-60min (faster than SU)
duration: 4-6hr (shorter than SU) |
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Term
| Which antidiabetic is the recommended first-line therapy by the ADA? |
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Definition
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Term
| T/F Good renal function is required to take metformin? |
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Definition
| True - excreted unchanged in the urine |
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Term
| T/F 33% of patients stop responding to metformin after 1.5 years of treatment. |
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Definition
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Term
| The effects of Thiazolidinediones (TZDs | rosiglitazone | pioglitazone) begin after ____ weeks. |
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Definition
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Term
| List 5 adverse reactions associated with Thiazolidinediones (TZDs | rosiglitazone | pioglitazone). |
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Definition
1. Hepatox (low risk)
2. Cholestyramine/colestipol inhibit absorption
3. Macular edema/retina swelling
4. 2X increased risk of bone fractures
5. CHF, MI (risk increased by 30-40%) |
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Term
| Acarbose more potently inhibits ________, while miglitol more potently inhibits __________ and _________. |
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Definition
Acarbose (Precose) = glycoamylase
Migitol (Glyset) = sucrase and maltase |
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Term
| List the two major side effects of a-glucosidase (Migitol|Carbose) inhibitors. |
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Definition
1. Liquid Poo
2. Farting...lots of farting |
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Term
| Why are combination therapies common in antidiabetic drugs? |
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Definition
1. 50% of pts immediately require a 2nd drug
2. After 3 years 75% of pts require a 2nd drug |
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Term
| What are the actions of amylin analogues (Symlin)? |
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Definition
1. suppresses glucagon release
2. delays gastric emptying
3. Suppresses appetite --> weight loss
4. decrease postprandial glucose conc. |
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Term
| How is an Amylin analogue (Symlin) useful it DB treatment? |
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Definition
| Amylin secretion is decreased in the pathophysiolgy of DB |
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Term
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Definition
| INtestinal seCRETion of INsulin hormones |
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Term
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Definition
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Term
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Definition
insulinotropic agent in Type 2 DB
Anti-apoptotic agent to beta cells of the pancreas islet - up-regulates pdx-1 |
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Term
| GLP-1 is useful in treating what type of DB? |
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Definition
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Term
| T/F GIP is used in the treatment of Type 2 DB? |
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Definition
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Term
| INCRETINs work best when administered (orally/injected) |
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Definition
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Term
| INCRETINs are rapidly degraded via |
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Definition
| DPP-IV = dipeptidyl peptidase-IV |
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Term
| Describe the unique features of exenatide (Byetta). |
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Definition
1. Made from lizard saliva
2. Resistant to DPP-IV
3. Effects similar to GLP-1
4. Acts ONLY in the presence of HYPERglycemia |
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Term
| Describe the MOA of exenatide (Byetta) |
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Definition
1. increases cAMP, Ca influx of beta cells causing insulin release
2. Suppresses glucagon
3. Decreases HbA1c (glucose tolerance)
4. Decreases food intake/body weight |
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Term
| What is the onset/duration of exenatide (Byetta)? |
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Definition
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Term
| What are the side effects of exenatide (Byetta)? |
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Definition
1. NVD (Nausea 45% decreases after 2 mo)
2. Hypoglycemia if coadministered w/ an SU agent
3. acute pancreatitis |
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Term
| What class is Exenatide (Byetta) |
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Definition
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Term
| When comparing the PK of DPP-IV inhibitors and GLP-1R agonists |
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Definition
| DPP-IV inhibitors are more favorable b/c of the wide therapeutic range (overdose is non-tox) |
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Term
| When comparing administration of DPP-IV inhibitors and GLP-1R agonists |
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Definition
| DPP-IV are injectable, while GP-1Rs are orally adminstered |
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Term
| When comparing duration of action in DPP-IV inhibitors and GLP-1R agonists |
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Definition
DPP-IV = short
GLP-1R = days-wks |
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