Term
| What is the principle stimulus of insulin secretion? |
|
Definition
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|
Term
| 2 phases of insulin secretion in a normal individual after IV glucose infusion |
|
Definition
Phase I--rapid rise and fall
Phase II--slower, more gradual increase |
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Term
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Definition
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Term
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Definition
| no rapid rise occurs--only a slow rising phase with a much smaller peak than that observe din normal individuals |
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Term
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Definition
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Term
| Insulin receptor stimulates ___________ or _________ of cell-specific intracellular signal transduction proteins. |
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Definition
| phosphorylation; dephosphorylation |
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Term
Some insulin-mediated changes occur in the __________ of the cell and take place within __________.
Some changes require translocation of mediators to the _________ and require __________. |
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Definition
cytoplasm; seconds to minutes
nucleus; hours to days |
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Term
| Where are insulin receptors located? |
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Definition
| plasma membrane of all cells in the body |
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Term
| Intracellular beta subunits have... |
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Definition
| tyrosine kinase enzyme activity |
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Term
| Insulin and glucagon act _________. |
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Definition
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Term
| Glucagon is secreted by the ________ in response to _______. |
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Definition
| alpha cells of the pancreas; glucose deficiency |
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|
Term
| Where is insulin produced and secreted from? |
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Definition
| beta cells in the pancreas |
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Term
|
Definition
required in type 1 DM
used in type 2 DM patients who do not respond adequately to diet and oral hypoglycemic agents |
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Term
| ________ insulin is widely available because of recombinant DNA technology. _______ and _________ insulins are almost never used. |
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Definition
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Term
| Duration of action of insulin preparations depends on... |
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Definition
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Term
|
Definition
ultra-short acting
injectable
genetically engineered to reduce aggregation |
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Term
| Prevention of aggregation leads to... |
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Definition
| more rapid onset and offset |
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Term
|
Definition
-short acting
-recombinant identical to human insulin
-slower onset, longer peak, slower offset that ultra-short acting |
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Term
| When should regular insulin be given? |
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Definition
|
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Term
|
Definition
-intermediate-acting insulin
-complex of insulin and protamine
-designed to be absorbed more slowly from injection site |
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Term
| Why does NPH contain protamine? |
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Definition
| requires proteolytic degradation of protamine for absorption of insulin |
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|
Term
|
Definition
-formulated to dissolve more slowly than the intermediate-acting insulins
-very slow onset and "peakless" action |
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Term
| Asn-B21 to Gly, two Arg to C-terminus |
|
Definition
insulin glargine
precipitates in tissues |
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Term
| Thr-B30 is replaced by myristic acid |
|
Definition
insulin detemir
increases aggregation and reversibly binds to plasma albumin |
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Term
| extended zinc insulin suspension |
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Definition
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Term
| Which insulin dosage regimen is rarely used? |
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Definition
| single daily dose of intermediate-acting insulin |
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|
Term
|
Definition
injections 2-3 times per day
mixture of regular and intermediate/long-acting |
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|
Term
| intensive insulin therapy |
|
Definition
basal with glargine or detemir
bolus of regular or ultra-short at meals |
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|
Term
|
Definition
2/3 total dose before breakfast
-2/3 of AM dose: NPH
-1/3 of AM dose: regular
1/3 total dose in evening
-1/3 PM dose before dinner: regular
-2/3 PM dose before bed: NPH |
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Term
|
Definition
| less than or equal to 6.5% |
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|
Term
| fasting self-monitored glucose target |
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Definition
|
|
Term
| post-prandial glucose target |
|
Definition
|
|
Term
|
Definition
0.3-0.5 units/kg/day
titrated to glycemic targets |
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|
Term
| What types of insulin are available via SQ infusion pumps? |
|
Definition
regular
aspart
glulisine
lispro
others are too insoluble |
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|
Term
| What causes the adverse reaction to insulin therapy? |
|
Definition
HYPOGLYCEMIA
-inappropriate dose
-mismatch of time of injection vs. food intake
-exercise-induced glucose demand |
|
|
Term
| signs and symptoms of hypoglycemia |
|
Definition
sweating, hunger, paresthesias, palpitations, tremor, anxiety
confusion, weakness, drowsiness, blurred vision, loss of conciousness |
|
|
Term
|
Definition
diminished insulin secretion
tissue resistance to insulin
enhanced glucagon
enhanced gluconeogenesis
obesity |
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|
Term
|
Definition
insulin secretagogues
oral hypoglycemic agents |
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|
Term
|
Definition
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|
Term
|
Definition
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
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|
Term
|
Definition
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|
Term
| mechanism of action for sulfonylureas |
|
Definition
block ATP-sensitive K+ channel
leads to depolarization and influx of Ca2+
results in insulin secretion |
|
|
Term
| extrapancreatic effects of sulfonylureas |
|
Definition
-indirectly increase tissue sensitivity to insulin (help overcome insulin resistance)
-help suppress hepatic glucose output
*MOA unknown* |
|
|
Term
| The success of sulfonlyureas depends on... |
|
Definition
functionality of beta cells
20-25% of patients fail to respond adequately |
|
|
Term
| possible adverse effect of sulfonylureas |
|
Definition
|
|
Term
longest acting SU
highest frequency of side effects
use cautiously in elderly and renal/hepatic impairement |
|
Definition
| chlorpropamide (1st gen SU) |
|
|
Term
| Why are 2nd generation sulfonylureas used much more than 1st generations? |
|
Definition
-equally efficacious
-more potent
-short half life, but effects last 12-24 hrs
-less severe/persistent hypoglycemia |
|
|
Term
| rare side effects of sulfonylureas |
|
Definition
| nausea, vomiting, cholestatic jaundice, hyponatremia, blood dyscrasias |
|
|
Term
| sulfonylurea drug interactions |
|
Definition
-disulfiram-like interaciton with EtOH (especially chlorpropramide)
-EtOH inhibits gluconeogenesis--can potentiate hypoglycemic response |
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|
Term
|
Definition
| non-sulfonylurea insulin releasing agent |
|
|
Term
| mechanism of action for nateglinide |
|
Definition
blocks ATP-sensitive K+ channel
binds at same site as sulfonlyureas and at an additional site |
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|
Term
| Nateglinide has a ________ half life and ______ action. |
|
Definition
|
|
Term
| When is nateglinide taken? |
|
Definition
|
|
Term
| adverse effects of nateglinide |
|
Definition
similar to sulfonylureas
EXPENSIVE |
|
|
Term
|
Definition
antihyperglycemic action, NOT hypoglycemic
"euglycemic" |
|
|
Term
| There is no risk of _________ with metformin. |
|
Definition
|
|
Term
| mechanism of action for metformin |
|
Definition
-dec. gluconeogenesis, dec. hepatic glucose output
-inc. insulin action, inc. glycolysis
-inc. uptake and utilization by muscle
-dec. intestinal absorption of glucose |
|
|
Term
| How is metformin usually given? |
|
Definition
monotherapy or added to SU or TZD
(step up to daily divided doses) |
|
|
Term
|
Definition
-no weight gain
-no hypoglycemia
-significant lipid lowering effect
-works in patients that are insulin resistant |
|
|
Term
| advantages of metformin over SUs and insulin in what populations |
|
Definition
obese
insulin-resistant patients |
|
|
Term
| metformin contraindications |
|
Definition
renal/hepatic insufficiency
cardiac failure
hypoxic lung disease |
|
|
Term
| side effects of metformin |
|
Definition
| anorexia, nausea, abdominal discomfort, diarrhea |
|
|
Term
| Why are combinations good? |
|
Definition
| combine insulin releasing effect of SU with increased glucose utilization and decreased hepatic glucose output of metformin |
|
|
Term
|
Definition
| combo of glyburide (SU) and metformin |
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|
Term
|
Definition
|
|
Term
|
Definition
| metformin + repaglinide (non-SU) |
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|
Term
|
Definition
| metformin + rosiglitazone (TZD) |
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|
Term
|
Definition
| alpha-glucosidase inhibitor |
|
|
Term
|
Definition
| alpha-glucosidase inhibitor |
|
|
Term
| mechanism of action for alpha-glucosidase inhibitors |
|
Definition
-inhibit digestion of complex sugars
-decrease sugar uptake after a meal |
|
|
Term
| adverse effects of alpha-glucosidase inhibitors |
|
Definition
-flatulence, GI upset (leads to poor acceptance and compliance)
-watch out for hypoglycemia when used with insulin or SU |
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|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
insulin sensitizers
EXPENSIVE |
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|
Term
| Why is there an increasing call to remove rosiglitazone (Avandia) from the market? |
|
Definition
|
|
Term
|
Definition
binds to nuclear transcription factors involved in insulin action
-dec. insulin resistance
-inc. peripheral action of insulin
-inc. glucose uptake
-dec. hepatic glucose output |
|
|
Term
| How long does it take for TZD to have clinical effect? |
|
Definition
|
|
Term
| Why are liver enzyme tests required with TZD use? |
|
Definition
| idiosyncratic hepatocellular injury |
|
|
Term
|
Definition
| Class III-IV heart failure patients |
|
|
Term
|
Definition
| increased risk of heart failure, angina, and MI |
|
|
Term
|
Definition
synthetic amylin analog
adjunct to insulin treatment (injectable) |
|
|
Term
| pramlintide mechanism of action |
|
Definition
suppression of glucagon release and hepatic glucose production
decreased post-prandial glucose levels |
|
|
Term
| Pramlintide is useful for... |
|
Definition
| type 1 and 2 diabetics requiring large amounts of insulin |
|
|
Term
| Pramlintide has an _______ effect. |
|
Definition
| anorectic (weight loss, decreased gastric emptying) |
|
|
Term
| Pramlintide is injected ___________ and is not mixed with ________. |
|
Definition
|
|
Term
|
Definition
GLP-1 analog
adjunct to metformin or SU or combo for type 2 DM |
|
|
Term
| exenatide mechanism of action |
|
Definition
enhances secretion of insulin
inhibits glucagon secretion |
|
|
Term
| adverse effects of exenatide |
|
Definition
recent reports of pancreatitis
rare cases of renal failure |
|
|
Term
|
Definition
newer GLP-1 agonist
almost identical to human GLP-1
30% greater effect on HbA1C than exenatide |
|
|
Term
|
Definition
dipeptidyl peptidase-4 inhibitor
adjunct with metformin, SU, or TZD |
|
|
Term
| sitagliptin mechanism of action |
|
Definition
| dipeptidyl peptidase-4 degrades GLP-1 and GIP (two incretins which increase insulin release, suppress glucagon release, and delay gastric emptying) |
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