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42 Cards in this Set
- Front
- Back
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Beginning with glucose uptake by the GLUT2 receptor, describe how insulin is secreted from pancreatic beta cells.
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(1) glucose is taken up by the beta cell
(2) glycolysis takes place; glucokinase increases the ATP/ADP ratio (3) more ATP causes K+ channels to close (4) depolarization occurs (5) there is an influx of calcium into the cell (6) secretory granules are released |
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Once insulin binds to its receptor and tyrosines on insulin receptor substrate proteins are phosphorylated, there are three possible biochemical pathways that can take place. Name them.
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(1) cell growth and differentiation, mediated by MAP kinase
(2) glucose, protein metabolism, mediated by P13 kinase (3) lipid synthesis, mediated by P13 kinase and protein kinase C |
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Why does the liver "see" a much higher insulin concentration than the rest of the body?
What is the significance of this? |
Insulin is secreted into the portal circulation and goes directly to the liver.
The significance of this is that 50% of insulin is destroyed in one pass through the liver. |
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Why does renal failure require changing a person's insulin dosing?
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The kidneys metabolize 30% of endogenous insulin and 60% of injected insulin.
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TRUE or FALSE
Insulin greatly increases glucose uptake in many tissues such as liver, muscle, brain and nerves. |
FALSE
Insulin increases glucose uptake in few cell types/organs. These include fat, liver and muscle AND NOT the brain or nerves. |
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Describe the etiology, onset and symptoms associated with IDDM.
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(1) Etiology: 50% genetic and 50% environmental
(2) Onset: rapid and usually occurs in people between the ages of 2 and 30yo (3) Symptoms: polyuria, polydipsia and polyphagia with weight loss and dec strength |
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Describe the etiology, onset and symptoms associated with NIDDM.
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(1) Etiology: insulin resistance often 2ndary to obesity and beta cell failure; genetic and environmental
(2) Onset: gradual; symptoms may be minimal or absent even though the disease progresses (3) Features: elevated fasting and/or post-prandial hyperglycemia |
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Compare insulin levels in IDDM and NIDDM.
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IDDM: almost complete lack of insulin
NIDDM: insulin resistance develops and insulin levels may be high to compensate for this resistance; beta cells become exhausted overtime and blood glucose levels will rise |
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How would you treat a patient with gestational diabetes?
Is she at an increased risk of developing diabetes in the future? |
Treat gestational diabets with injectable insulin.
Mothers with gestational diabetes are at an inc risk of developing NIDDM. |
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Controlling what 3 things can reduce diabetic complications?
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(1) tight blood glucose control
(2) blood pressure control (3) serum lipid control |
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What are the 4 main categories of primary complications in diabetic patients?
Which one is associated with the highest rate of mortality? |
(1) cardiovascular
(2) blindness (3) renal failure (4) neuropathy Cardiovascular complications are associated with the highest rate of mortality. |
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TRUE or FALSE
Tight blood glucose control reduces the occurrence of primary complications in diabetics -- especially the occurrence of cardiovascular events. |
FALSE
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What are the 3 main short-term goals of diabetes treatment?
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(1) relieve hyperglycemia
(2) overcome acute ketoacidosis (3) promote normal growth in kids |
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What are the 3 major indications for prescribing insulin?
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(1) IDDM
(2) NIDDM when diet alone or oral agents fail; or during periods of illness or stress (3) gestational diabetes |
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How are the various insulin preparations similar?
How are they different? |
They are similar in that they all act on the same insulin receptor.
They differ in their speed and duration of action. |
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TRUE or FALSE
All insulin preparations, as well as regular insulin, is given intravenously. |
FALSE
Insulin preparations are given subq by injection or pump. Regular insulin is given IV for ketacidosis. |
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The goal of insulin therapy is to be..
(a) at an intermediate level throughout the day (no fluctuation) (b) at low levels after meals and at high levels between meals (c) at high levels after meals and at low levels between meals |
The goal of insulin therapy is to be..
(c) at high levels after meals and at low levels between meals. |
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What are the 2 main problems with insulin therapy?
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(1) lipodystrophy and allergy to insulin
(2) hypoglycemia, which is common when maintaining tight control of blood glucose |
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What happens physiologically after a diabetic becomes hypoglycemic?
What are the signs/symptoms? How do you treat it? What could have caused the person to become hypoglycemic in the first place? |
Hypoglycemia is detected by the hypothalamus and leads to increased epinephrine production, which promotes glycogenolysis.
Symptoms of hypoglycemia include confusion, seizures and coma. The release of epinephrine and glycogenolysis causes increased HR, palpitations, sweating, hunger and weakness. Treat with oral or IV glucose. Causes of hypoglycemia include insulin overdose, exercise or skipped meals. |
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What "is" diabetic ketoacidosis? (what happens, what's the pathophysiology, etc)
How do you treat it? |
Diabetic ketoacidosis occurs in the setting of an extreme lack of insulin.
This causes dehydration and acidosis. Acidosis occurs due to increased lipolysis and conversion of fatty acids to acetoacetoacetate and beta hydroxybutyrate. Acidosis and dehydration leads to an electrolyte imbalance. Treatment: rapidly restore glucose uptake, reduce gluconeogenesis, stop ketone production, restore pH, normalize electrolytes; provide IV regular insulin and replace fluid and electrolytes |
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What is a hyperosmolar coma?
Are patients with IDDM or NIDDM more likely to suffer from this? |
Hyperosmolar coma is dehydration without ketoacidosis. It occurs in the setting of high glucose levels and extreme insulin deficiency.
Type II diabetics are more likely to suffer from this. |
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What are the main indications for oral diabetic therapy?
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Oral anti-diabetic drugs are prescribed for symptomatic type 2 diabetics who cannot control their diabetes with diet alone or who cannot/do not want to use insulin.
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Describe (in general) the mechanism of action of sulfonylurea anti-diabetic drugs.
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Sulfonylureas are insulin secretagogues.
They make the beta cell K+ channel more sensitive to ATP, leading to depolarization and more insulin secretion. |
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2nd generation sulfonylureas are contraindicated if the patient has this condition...
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2nd generation sulfonylureas are metabolized in the liver and are contraindicated with liver failure.
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What are the adverse effects associated with 2nd generation sulfonylureas?
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(1) hypoglycemia
(2) may lose efficacy over time (probably due to eventual inability of beta cells to respond) |
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Second generation sulfonylureas are given once daily.
What about other insulin secretagogues like replaginide? |
Replaginide has a short duration of action and is taken before meals (several times per day) when more insulin is needed.
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Describe (in general) the mechanism of action of biguanides.
What are benefits of biguanides? What are the adverse effects? |
Biguanides (ex: metformin) increases tissue glucose uptake and reduces hepatic gluconeogenesis, possibly by the activation of AMP kinase.
Benefits: delays or prevents onset of NIDDM; does not depend on insulin secretion; does not produce hypoglycemia; works well with other oral agents Adverse effets: GI distress; may promote lactic acidosis by unknown mechanism |
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Under what conditions is the risk of metformin-induced lactic acidosis increased?
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(1) ***alcohol**
(2) tissue hypoxia (3) overdose (4) renal failure |
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Describe the mechanism of action of thiazolidinediones (rosiglitazone, pioglitazone).
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They reduce insulin resistance by altering gene expression through PPAR-gamma receptor interaction.
Causes decreased TNF-alpha, increased adiponectin, and increased lipid storage. |
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What are the adverse effects associated with thiazolidinediones?
What are the contraindications? Can they delay or prevent NIDDM? |
Adverse effects: weight gain, fluid retention (can promote CHF) and hepatotoxicity
Contraindicated by pregnancy, hepatic failure, heart failure They may delay NIDDM. |
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Describe the mechanism of action of alpha-glucosidase inhibitors.
How should patients be instructed to take these drugs? |
These drugs inhibit alpha-glucosidase in the gut, slowing intestinal absorption of glucose from polysaccharides - which lowers post-prandial glucose peaks.
These drugs are taken orally with meals. |
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Pramlintide is an injectable analogue of this beta cell product.
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Pramlintide is an injectable analogue of amylin.
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What is the primary effect of the amylin agonist, pramlintide?
What is its major adverse effect? |
Amylin agonists reduce post-prandial glucose in Type 1 and Type 2 diabetics.
Major adverse effect is hypoglycemia. |
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List the actions of incretins.
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(1) inc insulin secretion
(2) inc beta cell growth (3) reduced glucagon secretion (4) slower gastric emptying (5) reduced appetite |
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What is the potential benefit of the incretin analogue, exenatide?
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A GLP-1 incretin analogue in animal models of IDDM can reverse diabetes if immune response is suppressed.
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What is the mechanism of action of the DPP IV inhibitor, sitagliptin?
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It blocks GLP-1 degradation (thus, maintaining the action of incretins).
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This peptide is stored in pancreatic beta cells and is co-secreted with insulin.
a) pramlintide b) amylin c) exenatide |
This peptide is stored in pancreatic beta cells and is co-secreted with insulin.
b) amylin |
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Describe amylin's effects.
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Amylin is co-secreted with insulin and has these effects..
1) slows gastric emptying 2) regulates postprandial glucagon 3) reduces food intake |
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Describe pramlintide's mechanism of action.
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Pramlintide is an analog of amylin and closely mimic's amylin's actions.
Pramlintide regulates postmeal blood glucose levels by slowing gastric emptying, promoting satiety, and suppressing the abnormal postprandial rise of glucagon in patients with diabetes. Thus, endogenous (liver-derived) and exogenous (meal-derived) glucose influx are better regulated, allowing exogenous insulin therapy to more easily match physiologic needs. |
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GLP-1 is a substrate for dipeptidyl peptidase IV.
What is GLP-1? What is the significane of dipeptidyl peptidase IV? |
GLP-1 is an incretin that is synthesized by the small intestine. Its major effect is to stimulate glucose-dependent insulin secretion.
GLP-1 exhibits a short half-life of one to two minutes due to N-terminal degradation by the enzyme dipeptidyl peptidase IV (DPP-IV). This necessitates continuous infusion of GLP-1 to achieve steady state levels in pharmacologic studies. Research has focused on GLP-1 like analogs that are resistant to DPP-IV degradation and on agents that increase GLP-1 via inhibition of DPP-IV. |
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Describe exenatide's mechanism of action.
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Exenatide is a GLP-1 analog that is resistant to DPP-IV degradation.
Exenatide exhibits dose dependent and glucose-dependent augmentation of insulin secretion |
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Match the following statements with either (a) exenatide (b) sitagliptin (c) liraglutide or (d) pramlintide
(1) Naturally occurring GLP-1 analog that is resistant to DPP-IV degradation. (2) Mimics the action of amylin so as to regulate postmeal blood glucose levels by slowing gastric emptying, promote satiety, and suppress the abnormal postprandial rise of glucagon in patients with diabetes. (3) Inhibitor of DPP-IV that is approved as initial pharmacologic therapy for the treatment of type 2 diabetes. (4) Synthetic GLP-1 analog that non-covalently binds to serum albumin through a lipid side chain, resulting in slower degradation by DPP-IV. |
(1) Naturally occurring GLP-1 analog that is resistant to DPP-IV degradation = EXENATIDE
(2) Mimics the action of amylin so as to regulate postmeal blood glucose levels by slowing gastric emptying, promote satiety, and suppress the abnormal postprandial rise of glucagon in patients with diabetes = PRAMLINTIDE (3) Inhibitor of DPP-IV that is approved as initial pharmacologic therapy for the treatment of type 2 diabetes = SITAGLIPTIN (4) Synthetic GLP-1 analog that non-covalently binds to serum albumin through a lipid side chain, resulting in slower degradation by DPP-IV. = LIRAGLUTIDE |
