Screening models for antidiabetic drugs are essential in B. Pharm education, linking pharmacology, pharmaceutics and drug discovery. This concise guide reviews in vitro models (beta‑cell lines, adipocytes, hepatocytes), in vivo rodent and genetic models (STZ, alloxan, db/db, ob/ob), and modern high-throughput screening, ADMET evaluation, pharmacodynamics, and toxicity screening. Students will learn key assays — insulin secretion ELISA, glucose uptake, OGTT, hyperinsulinemic-euglycemic clamp — and understand translational challenges, controls, biomarkers, and ethical 3Rs. Emphasis on mechanism-based targets (DPP‑4, PPARγ, GLP‑1) prepares B. Pharm students for practical screening strategies. Focus includes assay validation, positive and negative controls, statistical power and data interpretation for robust lead selection. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which pancreatic beta-cell line is commonly used to study insulin secretion in vitro?
- HepG2
- 3T3-L1
- INS-1
- L6
Correct Answer: INS-1
Q2. Which cell line is widely used as an adipocyte model for glucose uptake and insulin sensitivity studies?
- HEK293
- 3T3-L1
- MIN6
- C2C12
Correct Answer: 3T3-L1
Q3. Which hepatocyte-derived cell line is frequently used to study gluconeogenesis and hepatic glucose metabolism?
- HepG2
- INS-1
- 3T3-L1
- CHO
Correct Answer: HepG2
Q4. Which assay is commonly used to quantify cellular glucose uptake in screening antidiabetic compounds?
- 2-deoxyglucose uptake assay
- MTT cell viability assay
- ELISA for TNF-alpha
- Western blot for cytochrome P450
Correct Answer: 2-deoxyglucose uptake assay
Q5. Which method is the gold-standard for measuring insulin concentration in in vitro insulin secretion studies?
- Immunofluorescence staining
- Radioactive glucose uptake
- Insulin ELISA
- qPCR for insulin mRNA
Correct Answer: Insulin ELISA
Q6. Alpha-glucosidase inhibition screening primarily evaluates which mechanism?
- Increasing insulin secretion
- Delaying carbohydrate absorption in the gut
- Enhancing hepatic gluconeogenesis
- Stimulating insulin receptor expression
Correct Answer: Delaying carbohydrate absorption in the gut
Q7. Which enzymatic assay is used to identify potential DPP-4 inhibitor compounds?
- Acetylcholinesterase activity assay
- DPP-4 activity assay
- Catalase activity assay
- Glucokinase activity assay
Correct Answer: DPP-4 activity assay
Q8. Which chemical is commonly used to induce experimental diabetes by selective pancreatic beta-cell damage?
- Alloxan
- STZ (streptozotocin)
- DMSO
- Sucrose
Correct Answer: STZ (streptozotocin)
Q9. What is the primary mechanism by which alloxan induces beta-cell cytotoxicity?
- Inhibition of GLUT4 translocation
- Generation of reactive oxygen species (ROS) causing DNA damage
- Activation of PPARγ leading to adipogenesis
- Direct blockade of insulin receptor
Correct Answer: Generation of reactive oxygen species (ROS) causing DNA damage
Q10. Which genetic rodent model carries a leptin receptor mutation and is used to study type 2 diabetes and obesity?
- STZ-induced rat
- db/db mouse
- Alloxan mouse
- Wistar Kyoto rat
Correct Answer: db/db mouse
Q11. Which experimental technique is considered the gold standard to quantify whole-body insulin sensitivity in vivo?
- Oral glucose tolerance test (OGTT)
- Fasting blood glucose measurement
- Hyperinsulinemic-euglycemic clamp
- Homeostatic Model Assessment (HOMA-IR)
Correct Answer: Hyperinsulinemic-euglycemic clamp
Q12. The OGTT primarily assesses which physiological parameter?
- Basal hepatic insulin clearance
- Postprandial glucose handling and tolerance
- Muscle glycogen content
- Pancreatic alpha-cell function
Correct Answer: Postprandial glucose handling and tolerance
Q13. In chronic antidiabetic efficacy studies, which biomarker is most used to assess long-term glycemic control?
- Random plasma glucose
- HbA1c
- Serum insulin after meal
- Plasma C-peptide
Correct Answer: HbA1c
Q14. Which intracellular signaling event is often measured in high-throughput screens for insulin-mimetic activity?
- Phosphorylation of AKT
- Increase in caspase-3 activity
- Downregulation of GLUT2 mRNA
- Elevation of lactate dehydrogenase release
Correct Answer: Phosphorylation of AKT
Q15. Which drug is commonly used as a positive control in screens targeting insulin sensitization?
- Glibenclamide
- Metformin
- Atropine
- Propranolol
Correct Answer: Metformin
Q16. Which principle summarizes ethical animal use in screening studies?
- Test, Treat, Terminate
- Reduce, Refine, Replace
- Randomize, Repeat, Report
- Probe, Publish, Profit
Correct Answer: Reduce, Refine, Replace
Q17. What advantage do zebrafish models offer in antidiabetic drug screening?
- Identical physiology to humans
- Low-throughput but exact metabolism
- Transparent embryos enabling rapid in vivo phenotypic screening
- Require large compound quantities
Correct Answer: Transparent embryos enabling rapid in vivo phenotypic screening
Q18. Activation of which pathway leads to GLUT4 translocation in muscle and adipose cells?
- cAMP/PKA pathway
- PI3K/AKT pathway
- JAK/STAT pathway
- NF-κB pathway
Correct Answer: PI3K/AKT pathway
Q19. Which in vitro assay is commonly used to assess pancreatic beta-cell viability after compound exposure?
- Oil Red O staining
- MTT cell viability assay
- Chromatin immunoprecipitation
- Northern blotting
Correct Answer: MTT cell viability assay
Q20. Which in vivo parameter is a sensitive indicator of hepatotoxicity during antidiabetic drug screening?
- Serum ALT and AST levels
- Blood glucose after OGTT
- Urine glucose concentration
- Serum C-peptide
Correct Answer: Serum ALT and AST levels
Q21. Which ADME parameter is particularly critical for oral antidiabetic drug candidates?
- Dermal absorption
- Oral bioavailability
- Inhalation half-life
- Ocular permeability
Correct Answer: Oral bioavailability
Q22. Which assay is used to evaluate PPARγ agonist activity relevant to antidiabetic screening?
- Oil Red O staining for adipogenesis
- Glucose oxidase colorimetric assay
- Comet assay for DNA damage
- Patch-clamp recording
Correct Answer: Oil Red O staining for adipogenesis
Q23. Why are db/db mice useful for studying type 2 diabetes therapies?
- They have beta-cell ablation by toxins
- They carry a leptin receptor mutation causing obesity and insulin resistance
- They exhibit enhanced insulin sensitivity
- They are resistant to high-fat diet effects
Correct Answer: They carry a leptin receptor mutation causing obesity and insulin resistance
Q24. Compared to alloxan, why is streptozotocin (STZ) often considered more beta-cell selective?
- STZ is taken up preferentially by GLUT2-expressing beta cells
- STZ only affects adipose tissue
- Alloxan requires co-administration with insulin
- STZ inhibits GLP-1 receptors
Correct Answer: STZ is taken up preferentially by GLUT2-expressing beta cells
Q25. In a screen for insulin secretagogues, which result indicates a promising candidate?
- Decrease in insulin release at high glucose
- Increase in insulin release in response to glucose stimulation
- Unchanged insulin but increased lactate production
- Reduced cell viability with elevated insulin mRNA
Correct Answer: Increase in insulin release in response to glucose stimulation
Q26. Which assay is appropriate for primary screening of GLP-1 receptor agonists?
- cAMP accumulation assay
- LDH release assay
- Alpha-amylase activity
- ROS generation assay
Correct Answer: cAMP accumulation assay
Q27. Determining the minimum number of animals or replicates needed for reliable screening results requires which consideration?
- Intuition based on previous studies
- Power calculation based on effect size and variance
- Using at least 100 samples by default
- Choosing sample size after seeing initial data
Correct Answer: Power calculation based on effect size and variance
Q28. During preclinical screening, why must hypoglycemia risk be assessed for antidiabetic candidates?
- Hypoglycemia indicates increased renal clearance
- Severe hypoglycemia is a major clinical safety concern for glucose-lowering drugs
- Hypoglycemia enhances drug absorption
- It predicts hepatotoxicity
Correct Answer: Severe hypoglycemia is a major clinical safety concern for glucose-lowering drugs
Q29. A common barrier to translating in vitro antidiabetic findings to in vivo efficacy is:
- Excessive assay sensitivity that detects non-specific effects
- Metabolic instability leading to rapid conversion to inactive metabolites in vivo
- Inability to measure insulin in vitro
- Overexpression of GLUT4 in all cell lines
Correct Answer: Metabolic instability leading to rapid conversion to inactive metabolites in vivo
Q30. In high-throughput screening, which statistical metric indicates a robust and reliable assay?
- P-value > 0.05
- Z’-factor greater than 0.5
- Coefficient of variation above 50%
- Signal-to-noise ratio less than 1
Correct Answer: Z’-factor greater than 0.5
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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