Endocrine pharmacology: insulin action and signaling MCQs With Answer

Introduction:

This set of MCQs on Endocrine Pharmacology: Insulin Action and Signaling is designed specifically for M.Pharm students preparing for advanced pharmacology examinations. The questions probe molecular mechanisms of insulin receptor activation, downstream kinase cascades (PI3K–Akt, MAPK), GLUT4 trafficking, regulatory phosphatases, and mechanisms of insulin resistance relevant to drug action. Clinical and therapeutic implications — including how antidiabetic agents and pathological states modulate signaling nodes — are integrated to deepen understanding. Answers are provided to support self-assessment and targeted revision of signaling components, pharmacological modulators, and translational concepts relevant to research and advanced clinical pharmacology.

Q1. Which structural feature correctly describes the insulin receptor (IR)?

• Monomeric single polypeptide with intrinsic serine kinase activity
• Disulfide-linked heterotetramer composed of two alpha and two beta subunits with intrinsic tyrosine kinase activity
• G protein-coupled receptor that signals via cAMP
• Receptor tyrosine phosphatase that dephosphorylates insulin

Correct Answer: Disulfide-linked heterotetramer composed of two alpha and two beta subunits with intrinsic tyrosine kinase activity

Q2. Autophosphorylation of the insulin receptor following insulin binding primarily occurs on which residues of the beta subunit?

• Serine residues in the juxtamembrane region
• Tyrosine residues within the kinase activation loop
• Threonine residues in the C-terminal tail
• Histidine residues in the extracellular domain

Correct Answer: Tyrosine residues within the kinase activation loop

Q3. Insulin receptor substrates (IRS proteins) act as docking platforms by presenting which phosphorylated motif to downstream SH2-domain containing proteins?

• Phosphotyrosine-containing motifs
• Phosphoserine-rich motifs
• Polyubiquitinated lysine motifs
• Acetylated lysine motifs

Correct Answer: Phosphotyrosine-containing motifs

Q4. Activation of PI3K in insulin signaling requires recruitment via which regulatory interaction?

• Direct binding of PI3K catalytic p110 to insulin
• Binding of PI3K regulatory p85 subunit to phosphotyrosine residues on IRS proteins
• GTP-loading of Ras followed by direct PI3K activation
• Covalent modification of PI3K by ubiquitin ligase

Correct Answer: Binding of PI3K regulatory p85 subunit to phosphotyrosine residues on IRS proteins

Q5. The generation of PIP3 at the plasma membrane primarily serves to recruit which kinase for subsequent Akt activation?

• Protein kinase A (PKA)
• Phosphoinositide-dependent kinase-1 (PDK1)
• AMP-activated protein kinase (AMPK)
• SRC-family tyrosine kinases

Correct Answer: Phosphoinositide-dependent kinase-1 (PDK1)

Q6. Akt (protein kinase B) activation leads to inhibition of glycogen synthase kinase-3 (GSK3). What is the downstream metabolic consequence relevant to insulin action?

• Reduced glycogen synthesis due to GSK3 activation
• Increased glycogen synthesis via disinhibition of glycogen synthase
• Enhanced gluconeogenesis through FOXO activation
• Suppression of lipogenesis by direct inhibition of ACC

Correct Answer: Increased glycogen synthesis via disinhibition of glycogen synthase

Q7. Translocation of GLUT4 vesicles to the plasma membrane in adipose and muscle cells is mediated by phosphorylation of which Rab GTPase-activating protein?

• AS160 (TBC1D4)
• Rab5 GAP
• PTEN
• IRS-1

Correct Answer: AS160 (TBC1D4)

Q8. Serine phosphorylation of IRS proteins is generally associated with which effect on insulin signaling?

• Enhanced tyrosine phosphorylation and increased signaling
• Degradation or reduced ability to recruit PI3K, contributing to insulin resistance
• Activation of MAPK pathway exclusively
• Direct activation of GLUT4 independent of PI3K

Correct Answer: Degradation or reduced ability to recruit PI3K, contributing to insulin resistance

Q9. PTEN negatively regulates insulin signaling by which biochemical activity?

• Dephosphorylating phosphotyrosines on the insulin receptor
• Converting PIP3 back to PIP2 via lipid phosphatase activity
• Ubiquitinating IRS proteins for proteasomal degradation
• Phosphorylating Akt at inhibitory sites

Correct Answer: Converting PIP3 back to PIP2 via lipid phosphatase activity

Q10. Which pathway downstream of insulin primarily mediates mitogenic and growth responses rather than acute metabolic effects?

• PI3K–Akt pathway
• MAPK/ERK pathway via Grb2–SOS–Ras activation
• cGMP–PKG pathway
• JAK–STAT pathway

Correct Answer: MAPK/ERK pathway via Grb2–SOS–Ras activation

Q11. Metformin improves insulin sensitivity partly by activating which energy sensor that alters hepatic gluconeogenesis and insulin signaling?

• mTORC1
• AMP-activated protein kinase (AMPK)
• Protein kinase C theta (PKCθ)
• Insulin degrading enzyme (IDE)

Correct Answer: AMP-activated protein kinase (AMPK)

Q12. Chronic elevation of free fatty acids can cause insulin resistance by activating which kinase that promotes serine phosphorylation of IRS proteins?

• Protein kinase A (PKA)
• Protein kinase C (novel isoforms like PKCθ)
• Cyclin-dependent kinase 2 (CDK2)
• PDK1

Correct Answer: Protein kinase C (novel isoforms like PKCθ)

Q13. Thiazolidinediones (TZDs) improve insulin sensitivity primarily via activation of which nuclear receptor and by increasing levels of which adipokine?

• PPARα and increasing leptin
• PPARγ and increasing adiponectin
• LXRs and increasing resistin
• FXR and increasing TNF-α

Correct Answer: PPARγ and increasing adiponectin

Q14. Which enzyme is principally responsible for intracellular insulin degradation and clearance?

• Insulin degrading enzyme (IDE)
• Protein disulfide isomerase
• Pepsin
• HMG-CoA reductase

Correct Answer: Insulin degrading enzyme (IDE)

Q15. Alternative splicing of the insulin receptor gene produces IR-A and IR-B isoforms. Which statement about these isoforms is correct?

• IR-A preferentially binds insulin-like growth factor 1 (IGF-1) and is more mitogenic
• IR-B is intracellular and does not bind insulin
• IR-A is exclusively expressed in liver, IR-B in brain
• Both isoforms are identical in ligand specificity and function

Correct Answer: IR-A preferentially binds insulin-like growth factor 1 (IGF-1) and is more mitogenic

Q16. In the context of insulin receptor endocytosis, which cellular mechanism primarily mediates internalization of the activated receptor?

• Clathrin-mediated endocytosis
• Direct translocation across the membrane pores
• Autophagy-dependent engulfment
• Exosomal budding from the plasma membrane

Correct Answer: Clathrin-mediated endocytosis

Q17. Which of the following best describes how mTORC1 activity interfaces with insulin signaling?

• mTORC1 activation downstream of Akt promotes protein synthesis but chronic hyperactivation can cause feedback inhibition of insulin signaling via S6K-mediated serine phosphorylation of IRS proteins
• mTORC1 directly phosphorylates insulin to enhance its activity
• mTORC1 is upstream of the insulin receptor and required for insulin binding
• mTORC1 dephosphorylates PIP3 to terminate signaling

Correct Answer: mTORC1 activation downstream of Akt promotes protein synthesis but chronic hyperactivation can cause feedback inhibition of insulin signaling via S6K-mediated serine phosphorylation of IRS proteins

Q18. Which laboratory assay is most specific for assessing acute insulin-stimulated glucose uptake in isolated muscle or adipose tissue?

• Measuring plasma insulin concentration by ELISA
• 2-deoxyglucose uptake assay in tissue or cells
• Glycated hemoglobin (HbA1c) measurement
• Serum C-peptide level

Correct Answer: 2-deoxyglucose uptake assay in tissue or cells

Q19. In insulin-resistant states, which change in adipose tissue cytokine milieu contributes to impairing insulin signaling?

• Decreased TNF-α and increased adiponectin
• Increased TNF-α and decreased adiponectin
• Increased interleukin-10 and improved insulin sensitivity
• Decreased MCP-1 leading to improved insulin action

Correct Answer: Increased TNF-α and decreased adiponectin

Q20. Which pharmacological strategy directly targets an intracellular phosphatase to potentiate insulin signaling in experimental models?

• Inhibition of PTEN to increase PIP3 levels
• Activation of IDE to increase insulin degradation
• Inhibition of AMPK to reduce energy sensing
• Activation of PKCθ to promote IRS serine phosphorylation

Correct Answer: Inhibition of PTEN to increase PIP3 levels

Download