Diabetes Lecture Review Questions
REQUIRED READING: PANCREATIC HORMONES AND ANTI-DIABETIC DRUGS
Katzung’s Basic and Clinical Pharmacology
11th edition
Chapter 41, pp. 727-751
After this lecture, you should be able to answer the following:
1. What are the differences between Type 1 and Type 2 diabetes mellitus? What are some of the complications of diabetes mellitus? What are pancreatic islets? What types of islet cells make insulin? Islet amyloid polypeptide (IAPP)? Glucagon? Note: Be very comfortable with the slide dealing with glucose homeostasis and the effects of insulin.
2. What is preproinsulin? Proinsulin? Insulin?
3. Insulin receptor… made up of two alpha and two beta subunits. Alpha domains bind insulin. Beta domains have tyrosine kinase activity (able to put PO4 2- groups on tyrosine residues of protein substrates). Insulin binds… the Beta subunits of the insulin receptor are phosphorylated (auto phosphorylation)… this results in phosphorylation of IRS-1 (insulin receptor substrate 1) and Shc .. let’s just consider the events after that as “cell signaling” which results in mitogenesis, glycogen synthesis, lipid (triglyceride) synthesis and membrane trafficking of GLUCOSE TRANSPORTER 4 (in skeletal muscle and adipose tissue)
4. What is ketoacidosis? Can you smell acetone on the breath of severe Type 1 diabetics? Yes… because excess acetyl-CoA is being made into acetone and related compounds rather than being used to feed into the TCA cycle to make energy. KETONE BODIES (like acetone) are acidic and acidify the blood.. this can lead to diabetic ketoacidosis and coma.
5. GLUT2 is used by beta cells of the pancreas to determine whether or not to secrete insulin. NOTE: ALL TISSUES HAVE GLUT1.. be comfortable with the table listing the different GLUT transporters. Concentrate on the transporter, its tissue location, and its function.
6. Understand the role of Glucose intake through GLUT2 in beta cells… ATP production… closure of ATP-gated Potassium channels.. influx of calcium and release of insulin as the proposed mechanism of insulin release.
7. What happens to GLUT4 transporters when insulin levels rise. Where are they normally… where do they go? What happens to these transporters when insulin levels in blood decrease? Do GLUT4 transporters stay in the cell membrane? or do they return home.. back to the cytoplasm where they are contained in vesicles?
8. What are some of the metabolic effects of insulin on the liver? On the skeletal muscle? On fat cells?
9. What are the four major types of insulin preparations available? Is insulin administered orally? Why not? Does it have a long half-life?
10. Using these terms…. Hexamers… dimers… monomers…. Two amino acid change.. insulin…. Lispro…decreased hydrogen binding of insulin with itself… Explain to your study partner or a complete stranger who is willing to listen why lispro is rapid acting.
11. What effect does having zinc and acetate in the insulin preparation have on its abosorption? In other words.. what makes insulin intermediate- or long-acting?
More zinc favors more insulin in crystalline form which translates into slower absorption.
12. Protamine can be combined with regular insulin to make intermediate-acting insulin preparations. WHY does that work in slowing down absorption of regular insulin? This kind of intermediate-acting insulin is designated as NPH insulin.
13. Please be very familiar with the tables listing the different types of insulin preparations. Focus on the type.. the time to peak effect.. and the duration of action.
14. Is hypoglycemia the most common side effect of insulin therapy? Are all type 1 diabetics treated with insulin replacement? Is type 1 the result of beta pancreatic cell destruction?
15. What are the clinical indications for pramlintide? What are its chief pharmacological actions? What are its most relevant ADME parameters? Is there a boxed warning associated with this drug? What’s that all about?
16. Would you use sulfonylureas in Type 1 or Type 2 patients?? Think about the role of the beta cell in the action of these drugs,-- the answer is Type 2. Type 1s have low (or no) beta cells and hence little insulin to release.
17. Where do the sulfonylureas act? (inhibit the ATP-dependent K+ channel of beta cells). Be able to identify sulfonylureas such as first generation and second generation: NOTE: These drugs can induce hypoglycemia…..nausea, diarrhea & vomiting.
The following link is interesting: http://www.mja.com.au/public/issues/180_02_190104/vei10508_fm.html
It provides some case studies and things to think about in patients using sulfonylureas.
Please read the article. It’s not required… but suggested.
18. Meglitinides cause insulin release from beta cells. Two major meglitinides- repaglinide & nateglinide. How do they work? adverse effects? Receptor binding sites?
19. Do biguanides such as phenformin and metformin increase glucose uptake into skeletal muscle? (YES) What is lactic acidosis and is it related to metformin use, especially in patients with liver disease, renal impairment and cardiopulmonary insufficiency?
20. Understand the relationship of rosiglitazone and the receptor for PPARgamma (peroxisome proliferators activated receptor- gamma).
Rosiglitazone can activate PPARgamma receptor, a nuclear receptor which regulates expression of insulin-responsive genes involved in the control of glucose production, transport and utilization.
21. Chromium… understand that it may be involved in glucose tolerance and may help patients with type 2.
22. Alpha-glucosidase inhibitors. HOW DO THEY WORK? Inhibit break down of oligosaccharides to monosaccharides in the intestine by inhibiting alpha-glucosidase. Acarbose is one drug that belongs to this class. Flatulence, diarrhea and abdominal pain are COMMONLY seen in patients taking acarbose.
23. Glucagon is the physiological antagonist to insulin made by alpha cells of the pancreatic islet. Is glucagon often elevated in patients with Type 2 diabetes?
24. How does exenatide work? Adverse effects? Receptor binding sites.
25. Incretin mimetics. Adverse effects? Mechanism of action?
26. DPP-IV inhibitors. Adverse effects? Mechanism of action?
Katzung’s Basic and Clinical Pharmacology
11th edition
Chapter 41, pp. 727-751
After this lecture, you should be able to answer the following:
1. What are the differences between Type 1 and Type 2 diabetes mellitus? What are some of the complications of diabetes mellitus? What are pancreatic islets? What types of islet cells make insulin? Islet amyloid polypeptide (IAPP)? Glucagon? Note: Be very comfortable with the slide dealing with glucose homeostasis and the effects of insulin.
2. What is preproinsulin? Proinsulin? Insulin?
3. Insulin receptor… made up of two alpha and two beta subunits. Alpha domains bind insulin. Beta domains have tyrosine kinase activity (able to put PO4 2- groups on tyrosine residues of protein substrates). Insulin binds… the Beta subunits of the insulin receptor are phosphorylated (auto phosphorylation)… this results in phosphorylation of IRS-1 (insulin receptor substrate 1) and Shc .. let’s just consider the events after that as “cell signaling” which results in mitogenesis, glycogen synthesis, lipid (triglyceride) synthesis and membrane trafficking of GLUCOSE TRANSPORTER 4 (in skeletal muscle and adipose tissue)
4. What is ketoacidosis? Can you smell acetone on the breath of severe Type 1 diabetics? Yes… because excess acetyl-CoA is being made into acetone and related compounds rather than being used to feed into the TCA cycle to make energy. KETONE BODIES (like acetone) are acidic and acidify the blood.. this can lead to diabetic ketoacidosis and coma.
5. GLUT2 is used by beta cells of the pancreas to determine whether or not to secrete insulin. NOTE: ALL TISSUES HAVE GLUT1.. be comfortable with the table listing the different GLUT transporters. Concentrate on the transporter, its tissue location, and its function.
6. Understand the role of Glucose intake through GLUT2 in beta cells… ATP production… closure of ATP-gated Potassium channels.. influx of calcium and release of insulin as the proposed mechanism of insulin release.
7. What happens to GLUT4 transporters when insulin levels rise. Where are they normally… where do they go? What happens to these transporters when insulin levels in blood decrease? Do GLUT4 transporters stay in the cell membrane? or do they return home.. back to the cytoplasm where they are contained in vesicles?
8. What are some of the metabolic effects of insulin on the liver? On the skeletal muscle? On fat cells?
9. What are the four major types of insulin preparations available? Is insulin administered orally? Why not? Does it have a long half-life?
10. Using these terms…. Hexamers… dimers… monomers…. Two amino acid change.. insulin…. Lispro…decreased hydrogen binding of insulin with itself… Explain to your study partner or a complete stranger who is willing to listen why lispro is rapid acting.
11. What effect does having zinc and acetate in the insulin preparation have on its abosorption? In other words.. what makes insulin intermediate- or long-acting?
More zinc favors more insulin in crystalline form which translates into slower absorption.
12. Protamine can be combined with regular insulin to make intermediate-acting insulin preparations. WHY does that work in slowing down absorption of regular insulin? This kind of intermediate-acting insulin is designated as NPH insulin.
13. Please be very familiar with the tables listing the different types of insulin preparations. Focus on the type.. the time to peak effect.. and the duration of action.
14. Is hypoglycemia the most common side effect of insulin therapy? Are all type 1 diabetics treated with insulin replacement? Is type 1 the result of beta pancreatic cell destruction?
15. What are the clinical indications for pramlintide? What are its chief pharmacological actions? What are its most relevant ADME parameters? Is there a boxed warning associated with this drug? What’s that all about?
16. Would you use sulfonylureas in Type 1 or Type 2 patients?? Think about the role of the beta cell in the action of these drugs,-- the answer is Type 2. Type 1s have low (or no) beta cells and hence little insulin to release.
17. Where do the sulfonylureas act? (inhibit the ATP-dependent K+ channel of beta cells). Be able to identify sulfonylureas such as first generation and second generation: NOTE: These drugs can induce hypoglycemia…..nausea, diarrhea & vomiting.
The following link is interesting: http://www.mja.com.au/public/issues/180_02_190104/vei10508_fm.html
It provides some case studies and things to think about in patients using sulfonylureas.
Please read the article. It’s not required… but suggested.
18. Meglitinides cause insulin release from beta cells. Two major meglitinides- repaglinide & nateglinide. How do they work? adverse effects? Receptor binding sites?
19. Do biguanides such as phenformin and metformin increase glucose uptake into skeletal muscle? (YES) What is lactic acidosis and is it related to metformin use, especially in patients with liver disease, renal impairment and cardiopulmonary insufficiency?
20. Understand the relationship of rosiglitazone and the receptor for PPARgamma (peroxisome proliferators activated receptor- gamma).
Rosiglitazone can activate PPARgamma receptor, a nuclear receptor which regulates expression of insulin-responsive genes involved in the control of glucose production, transport and utilization.
21. Chromium… understand that it may be involved in glucose tolerance and may help patients with type 2.
22. Alpha-glucosidase inhibitors. HOW DO THEY WORK? Inhibit break down of oligosaccharides to monosaccharides in the intestine by inhibiting alpha-glucosidase. Acarbose is one drug that belongs to this class. Flatulence, diarrhea and abdominal pain are COMMONLY seen in patients taking acarbose.
23. Glucagon is the physiological antagonist to insulin made by alpha cells of the pancreatic islet. Is glucagon often elevated in patients with Type 2 diabetes?
24. How does exenatide work? Adverse effects? Receptor binding sites.
25. Incretin mimetics. Adverse effects? Mechanism of action?
26. DPP-IV inhibitors. Adverse effects? Mechanism of action?
posted by Blase Billack, Ph.D. | 7:18 AM
0 Comments:
Post a Comment
<< Home