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67 Cards in this Set
- Front
- Back
- 3rd side (hint)
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% Islet cells make up, % of total blood flow?
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2%
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15% BF
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% Beta cells make up in pancreas? % gamma?
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60% beta
(alpha = 25%) |
10% gamma
(<5% delta) |
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10th cranial nerve on pancreas?
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increases digestive & islet hormone secretion
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T5-T8 ganglia on pancrease?
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inhibs basal & glucose stimulated insulin secretion; SS secretion
stims glucagon & PP secretion |
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Epinephrine stims release of glucagon the _____; while it suppresses insulin release (from beta cells) thru _____.
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Beta-2 adrenergic mechanism
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Alpha-2 adrenergic mechanism
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What 2 tissues are the target for glucagon?
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liver
adipose tissue |
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What 3 things does glucagon do in order?
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1. causes glycogenolysis (breaks down stores)
2. cause gluconeogenesis (create more glucose) 3. inhibits glycolysis |
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T/F. Ketoacids inhibit glucagon secretion.
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true
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T/F. Insulin promotes protein uptake into cells and the conversion of AA into protein.
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True
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Amylin suppresses the ____ secretion of glucagon and slows down gastic emptying.
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postprandial
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Circulating amylin is low in type __ DM's, and impaired in type ___.
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1
(prob = absent since Beta cells destroyed) |
2
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This is the sensor for glucose at beta-cells.
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GLUT-1
(high or low affinity for glucose?) |
low
(only really works when glucose levels high) |
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Rate limiting step in lowering of BG?
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Glucokinase
(makes glucose phophylated; inc ATP) |
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High ATP ___ the ATP-sensitive K+ channel. Causing what?
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inhibits
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no K+ influx --> beta cell depolarization --> Ca2+ influx --> release of insulin
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Where do sulfonylureas bind?
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at the SUR1 site (acting like ATP and blocking the K+ influx)
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High functioning mutations of SUR1/Kir6.2 causes what? What about low functioning?
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too much activity --> hyperpolarization of beta cell --> too little insulin release --> DM!!!
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small activity --> constant depolarization of beta cell --> too much insulin release --> HYPOGLYCEMIA
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What binds to the G2 coupled receptors on beta cells?
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glucagon
GLP-1 GIP (these are incretin hormones) |
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What binds to the Gi GPCR's in the beta cell?
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somatostatin
alpha-2 adrenergic |
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What binds to the Gq GPCR's in the beta cell?
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muscarinic Ach
CCK (cholecystokinin) |
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IRS activation causes ____ to move towards the cell surface.
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GLUT-4
(high or low affinity?) |
high affinity for glucose; so brings glucose in even at low concentrations
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Insulin increases GLUT-4 transporters in what 2 specific tissues?
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adipocytes
muscle |
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T/F. Glucagon and GLP-1 are derived from different precursors.
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False
(from the same) |
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GLP-1 are from the intestinal ____. GIP are from ___.
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L-cells
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K-cells
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GLP-1 receptor is a ___ GPCR.
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Gs
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Chronic pancreatic GLP-1 R agonism leads to what?
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pancreatitis
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GLP-1 is ___ dependent.
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glucose
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SS is particularly released from ___ rich meal.
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protein
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This insulin is a monomer at low concentrations.
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native (regular) insulin
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This insulin retain the monomeric or dimeric conformation.
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analogs
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This analog reverses B28 and B29 (pro and lys); self associates into hexamers and can dec A1C by 1%.
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Insulin lispro (humalog)
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What site does Insulin Aspart change on the B-chain?
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B28
changes Pro to Asp |
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This insulin replaces site B3 with Lys and site B29 with Glu.
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Insulin glulisine (apidra)
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NPH is a suspension of native insulin with Zn and _____ in phosphate with ______.
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protamine
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m-cresol
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What does the m-cresol do to NPH?
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causes crystallizations so dissolves more gradually when SQ injected
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What alterations are made with Insulin glargine?
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A chain:site A21 is changed to Glycine
B chain: 2 Arg's are added to the C-terminus |
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What pH is Lantus formulated in? Benefit?
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4
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stabilizes the hexamer
(makes depo = long duration) |
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What receptor does Lantus bind to with more affinity than human insulin? What could be a result?
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IGF-1
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cell growth --> malignancy
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Insulin determir adds what to site B-29? Result?
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N-myristoyl (C=14)
fatty acid |
binds to albumin; increases duration to long acting
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Do sulfonylureas decerase hepatic clearance of insulin? Why?
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yes
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bc it further increases insulin levels
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What drugs can displace sulfonylureas from protein?
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ASA, NSAIDs, Warfarin, BB's, AB's, fibrates, EtOH and MAOIs
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Lipophilicity at R groups of sulfonylureas does what? What about lipophilicity and bulk?
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adds potency
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increases affinity
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Brand name for Repaglinide? How is it metabolized?
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Prandin
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CYP3A4 - 90%
kidneys - 10% |
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Brand name for Netaglinide? How is it metbolized?
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Starlix
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CYPs
(2C9>3A4) |
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Main use for Starlix? When does it markedly diminished effect?
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postprandial glucose in T2 DM's
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in the prescense of normglycemia (so no hypoglycemia)
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Metformin's MOA? Does it work on the pancreas?
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activates AMP-dependent protein kinase (AMPK)
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no - nonbeta cell acting drug
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Metformin's tranport of glucose into cells is mediated by ____. Why does the drug cause acidosis?
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OCT
Organic Cation Transporters |
bc it blocks gluconeogenesis and thus can impair hepatic metabolism
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Which diabetic drug causes a shift of lipid stores from extra-adipose to adipose tissue?
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Glitazone
(activate PPARgamma receptors) |
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Thiazolidinediones are ___ dependent.
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insulin
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Exenatide Brand? How often given?
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Byetta
(GLP-1 Agonist) |
injected BID before meals
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Liraglutide Brand? What's its most important change?
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Victoza
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has a L-16 fatty acid added to its backbone; causes it to bind to albumin --> long duration
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Which one is better at lowering A1C but alos has more nausea associated with it: Liraglutide or Exenatide?
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Exenatide (Byetta)
the synthetic exendin-4 |
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Why does Victoza have a black-box warning?
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it has been shown to increase risk of thyroid C-cell tumors in rodents
(so CI in pts with MTC hx) NOT 1st LINE!! |
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How much GLP-1 is active in the presence of DPP-4 inhib?
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100%
(vs 10-20% without) |
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Is Januiva a competitive inhibitor? Where is it absorbed?
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yes
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intestines
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What 2 things is DPP-4 critical to?
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T-lymphocyte function
suppression of tumors |
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How do alpha-glucosidase inhibitors work?
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by inhibiting the tranporter of glucose from intestines into brush border; also increases GLP-1 from unknown activity
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Acarbose brand? It is minimally absorbed?
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Precose
(alpha-glucosidase inhibitor) |
yes
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Miglitol brand? Is it minimally absorbed?
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Glyset
(alpha-glucosidase inhibitor) |
no
50-100% bioavailbale |
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Are alpha-glucosidase inhibitors used fro mono-therapy for DM?
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no, as adjunct
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Brand for Pramlintide? What does is seem to do?
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Symlin
(synthetic derivative of amylin) |
act's amylin recptors seem to:
reduce glucagon release delay gastric emptying satiety (use as an adjunct) |
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Where is GPR120 located? What does it secrete?
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intestinal L-cells
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GLP-1
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What normally binds to GPR120's?
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DHA, EPA, and ALA
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Brand for glyburide? Dose for glyburide?
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Micronase, Diabeta
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1.25-20 mg po qd
(start at 2.5-5 or 1.25 if hypo) (max = 20) |
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CrCl cut off for glyburide? Metformin?
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<50
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<60
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Brand for glimepiride? Dose?
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Amaryl
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1-4 mg po qd
(start at 1-2, inc 1-2 mg every 1-2 weeks // max 8 mg qd) |
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Brand for glipizide? Dose?
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Glucotrol
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2.5-20 mg po qd
(start at 5 or 2.5 if elderly; max 40 mg day; 30 min b4 meals) |
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CrCl restirictions for glipizide?
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if CrCl <50 decrease dose by 50%
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