Two hormones primarily keep blood glucose near 80–100 mg/dL and coordinate fuel storage/mobilization:
A. Insulin and cortisol
B. Insulin and glucagon
C. Glucagon and epinephrine
D. Insulin and growth hormone

B. Insulin and glucagon

After a high-carbohydrate meal, plasma insulin is typically highest at:
A. 5–10 minutes
B. 15–20 minutes
C. 60–90 minutes
D. 30–45 minutes

D. 30–45 minutes

Intertissue metabolic homeostasis is achieved in three principal ways; which is NOT one of them?
A. Lymphatic metabolite signaling
B. Blood nutrient concentration
C. Hormonal messaging
D. CNS neural control

A. Lymphatic metabolite signaling

Major determinant of whether skeletal muscle oxidizes fatty acids vs glucose:
A. Plasma lactate level
B. Hepatic glycogen content
C. Plasma fatty acid level
D. Portal glucagon level

C. Plasma fatty acid level

Adult minimum daily glucose requirement is best matched by:
A. 190 total, 150 brain, 40 others
B. 150 total, 80 brain, 70 others
C. 100 total, 40 brain, 60 others
D. 190 total, 100 brain, 90 others

A. 190 total, 150 brain, 40 others

Injected glucagon increases hepatic output but not skeletal muscle metabolism because muscle:
A. Uses only ketones
B. Degrades cAMP rapidly
C. Lacks glucagon receptors
D. Lacks pancreatic blood flow

C. Lacks glucagon receptors

Physiologic targets of glucagon include:
A. Brain and muscle
B. Liver and adipose
C. Kidney and bone
D. Muscle and heart

B. Liver and adipose

Poorly controlled diabetes causes weight loss despite appetite because:
A. Increased glycogen storage
B. Reduced FA oxidation
C. Increased glucose entry
D. Lipids become main fuel

D. Lipids become main fuel

Marked hyperglycemia causes polyuria → dehydration → higher glucose; the initial urine increase is from:
A. Osmotic diuresis
B. Water diuresis
C. Pressure natriuresis
D. Tubular necrosis

A. Osmotic diuresis

Confusion and seizures during severe hypoglycemia are:
A. Cholinergic manifestations
B. Neuroglycopenic manifestations
C. Osmotic manifestations
D. Myopathic manifestations

B. Neuroglycopenic manifestations

Tremor, palpitations, and sweating during hypoglycemia are driven mostly by:
A. Cortisol
B. Glucagon
C. Epinephrine
D. Insulin

C. Epinephrine

Correct islet hormone pairing:
A. α:glucagon β:insulin
B. α:insulin β:glucagon
C. α:amylin β:glucagon
D. α:insulin β:somatostatin

A. α:glucagon β:insulin

Islet hormones enter the liver first via:
A. Splenic vein
B. Inferior vena cava
C. Thoracic duct
D. Hepatic portal vein

D. Hepatic portal vein

Insulin is considered anabolic because after carbohydrate ingestion it promotes:
A. Lipolysis and ketogenesis
B. Glycogenolysis plus gluconeogenesis
C. Fuel use; fat and glycogen storage
D. Proteolysis and ketone use

C. Fuel use; fat and glycogen storage

Insulin and glucagon are synthesized in islet cells as:
A. Steroids
B. Prohormones
C. Amines
D. Eicosanoids

B. Prohormones

Preproinsulin is converted to proinsulin in the:
A. Rough ER
B. Golgi
C. Cytosol
D. Secretory granules

A. Rough ER

During proinsulin folding, disulfide bonds form between:
A. Lysine residues
B. Serine residues
C. Histidine residues
D. Cysteine residues

D. Cysteine residues

After folding and disulfide formation, proinsulin is transported to the:
A. Nucleus
B. Mitochondria
C. Golgi complex
D. Peroxisome

C. Golgi complex

Proteolysis in storage vesicles produces insulin plus:
A. C-peptide
B. Signal peptide
C. Protein kinase A
D. cAMP

A. C-peptide

Within storage vesicles, insulin is precipitated with:
A. Ca2+
B. Zn2+
C. Fe3+
D. Mg2+

B. Zn2+

Biologically active insulin consists of:
A. Single chain, no bonds
B. Three chains, peptide links
C. Two chains, peptide bond
D. Two chains, disulfide links

D. Two chains, disulfide links

Insulin binding triggers receptor autophosphorylation and downstream protein phosphorylation through the receptor’s:
A. Serine kinase domain
B. GPCR domain
C. Tyrosine kinase domain
D. Guanylyl cyclase domain

C. Tyrosine kinase domain

Glucagon raises cAMP, which activates PKA to:
A. Phosphorylate regulatory enzymes
B. Dephosphorylate regulatory enzymes
C. Cleave C-peptide
D. Insert GLUT4 channels

A. Phosphorylate regulatory enzymes

Compared with glucagon, insulin generally shifts key enzymes toward:
A. Increased phosphorylation
B. Increased cAMP
C. Increased PKA activity
D. Increased dephosphorylation

D. Increased dephosphorylation

Recurrent fasting hypoglycemia with inappropriately high insulin suggests a tumor producing excess insulin called:
A. Glucagonoma
B. Insulinoma
C. Somatostatinoma
D. VIPoma

B. Insulinoma

During IV glucose, β-cell uptake primarily uses:
A. GLUT1
B. GLUT2
C. GLUT4
D. SGLT2

B. GLUT2

In β-cells, glucose → glucose-6-phosphate via:
A. Hexokinase I
B. PFK-1
C. Glucose-6-phosphatase
D. Glucokinase

D. Glucokinase

β-cell glycolysis→TCA→OXPHOS most directly increases:
A. ATP levels
B. IP3 levels
C. NADPH levels
D. cAMP levels

A. ATP levels

Teen with new DKA has near-zero insulin. Best mechanism?
A. Increased hepatic insulin clearance
B. Peripheral insulin resistance
C. Autoimmune β-cell destruction
D. Excess autonomic vagal tone

C. Autoimmune β-cell destruction

Type 1 DM susceptibility is linked to HLA coding:
A. MHC II
B. MHC I
C. CD8 co-receptor
D. TCR beta chain

A. MHC II

Fasting hypoglycemia suggests insulinoma. As glucose falls:
A. Insulin falls appropriately
B. Insulin rises despite low glucose
C. Insulin becomes undetectable
D. Glucagon falls despite stress

B. Insulin rises despite low glucose

Approximate glucose threshold for insulin release:
A. 50 mg/dL
B. 60 mg/dL
C. 70 mg/dL
D. 80 mg/dL

D. 80 mg/dL

Insulin is rapidly removed primarily by:
A. Skeletal muscle
B. Liver
C. Brain
D. Pancreas

B. Liver

Cephalic-phase insulin release is enhanced by:
A. Somatic motor efferents
B. Dorsal root afferents
C. Vagus parasympathetic signals
D. Corticospinal tract firing

C. Vagus parasympathetic signals

Post-meal hormones that augment early insulin release:
A. GIP and GLP-1
B. Secretin and motilin
C. CCK and gastrin
D. Ghrelin and leptin

A. GIP and GLP-1

MODY can result from mutations in:
A. GLUT4 translocation proteins
B. Glucagon receptor subunits
C. Glucokinase or transcription factors
D. Insulin degradation enzymes

C. Glucokinase or transcription factors

MODY2 glucokinase mutation reduces activity via:
A. Lower Km and higher Vmax
B. Higher Km and higher Vmax
C. Lower Km and lower Vmax
D. Higher Km or lower Vmax

D. Higher Km or lower Vmax

Neonatal diabetes presents within the first:
A. Two weeks
B. First three months
C. First twelve months
D. First two years

B. First three months

Most common mutation in permanent neonatal diabetes:
A. KCNJ11
B. HLA-DQ
C. PFKM
D. GLUT4

A. KCNJ11

A KATP channel stuck open impairs insulin because:
A. ATP cannot be generated
B. GLUT2 cannot transport glucose
C. Proinsulin cannot fold
D. Ca2+ influx stays low

D. Ca2+ influx stays low

Glucagon is cleared by liver/kidney; half-life is:
A. 30–60 minutes
B. 10–20 minutes
C. 3–5 minutes
D. 1–2 hours

C. 3–5 minutes

Islet blood flow carries insulin:
A. δ→β across islet
B. β→α across islet
C. α→β across islet
D. Uniform bidirectional mixing

B. β→α across islet

Glipizide increases insulin secretion by:
A. Opening KATP channels
B. Blocking Ca2+ channels
C. Closing KATP channels
D. Inhibiting hepatic insulinase

C. Closing KATP channels

High insulin with absent C-peptide suggests:
A. Exogenous insulin use
B. Insulinoma secretion
C. MODY2 glucokinase defect
D. Type 2 insulin resistance

A. Exogenous insulin use

Primary defect in type 2 diabetes mellitus:
A. Autoimmune β-cell destruction
B. Absent insulin receptor synthesis
C. Defective portal vein delivery
D. Insulin resistance in tissues

D. Insulin resistance in tissues

In diabetes, glucagon may remain elevated due to:
A. Excess insulin feedback
B. Alpha-cell insulin resistance
C. Complete liver failure
D. Increased β-cell blood flow

B. Alpha-cell insulin resistance

NOT a plasma-membrane signaling mechanism:
A. Nuclear receptor transcription
B. Adenylate cyclase → cAMP
C. Receptor kinase activity
D. PIP2 hydrolysis coupling

A. Nuclear receptor transcription

Insulin receptor component spanning into cytosol:
A. Alpha subunit
B. C-peptide chain
C. Beta subunit
D. HLA subunit

C. Beta subunit

After insulin binding, phosphorylated IRS-1 recruits via:
A. PDZ domains
B. SH3 domains
C. WD repeats
D. SH2 domains

D. SH2 domains

Increased amino acid uptake into skeletal muscle primarily reflects which insulin action?
A. Growth factor–mediated protein synthesis
B. Stimulation of glucose and amino acid transport
C. Reverses glucagon phosphorylation
D. Alters enzyme gene expression

B. Stimulation of glucose and amino acid transport

A patient takes a methylxanthine PDE inhibitor. Which metabolic pattern is most expected?
A. Fed-state fuel storage
B. Fasted-state fuel mobilization
C. Ketone suppression
D. Glycolysis inhibition

B. Fasted-state fuel mobilization

A patient develops tachycardia after sympathetic surge. The dominant cardiac adrenergic receptor is:
A. β1 receptor
B. β3 receptor
C. α1 receptor
D. β2 receptor

A. β1 receptor

The major agonist stimulating the heart’s dominant β-receptor is:
A. Dopamine
B. Epinephrine
C. Norepinephrine
D. Acetylcholine

C. Norepinephrine

A hepatic cell increases glycogenolysis via an adrenergic receptor class most associated with fuel mobilization. Which receptor?
A. β3 receptor
B. β2 receptor
C. α1 receptor
D. β1 receptor

B. β2 receptor

Which catecholamine is a much more potent β2 agonist?
A. Epinephrine
B. Norepinephrine
C. Dopamine
D. Acetylcholine

A. Epinephrine

Activation of β2 receptors also mediates vascular, bronchial, and uterine smooth muscle ______.
A. Contraction
B. Necrosis
C. Calcification
D. Fibrosis

A. Contraction

A drug aimed at increasing thermogenesis in adipose tissue would target:
A. α1 receptor
B. β2 receptor
C. β1 receptor
D. β3 receptor

D. β3 receptor

β3 receptor activation most directly increases:
A. Fatty acid oxidation
B. Glycolysis rate
C. Glycogen synthesis
D. Protein catabolism

A. Fatty acid oxidation

Postsynaptic receptors mediating vascular contraction via Gq/PLCβ use:
A. cAMP cascade
B. PIP2 pathway
C. JAK-STAT signaling
D. Guanylyl cyclase

B. PIP2 pathway

In a healthy person after a high-carb meal, insulin peaks at 30–45 minutes and returns to basal by:
A. 30 minutes
B. 6 hours
C. 2 hours
D. 24 hours

C. 2 hours

Two insulin polypeptide chains are linked by:
A. Glycosidic bonds
B. Phosphodiester bonds
C. Peptide bonds
D. Disulfide bonds

D. Disulfide bonds

The insulin chain containing an additional intrachain disulfide bond is the:
A. β chain
B. A (α) chain
C. B (β) chain
D. Connecting peptide

B. A (α) chain

Increased β-cell glucose metabolism raises ATP:ADP, which first leads to:
A. Opening KATP channels
B. Closing KATP channels
C. Closing Ca2+ channels
D. Opening Cl− channels

B. Closing KATP channels

Closure of β-cell KATP channels most directly causes:
A. Membrane hyperpolarization
B. Membrane depolarization
C. Ribosomal translocation
D. MHC II expression

B. Membrane depolarization

Insulin is rapidly cleared primarily by the:
A. Liver
B. Brain
C. Pancreas
D. Skin

A. Liver

Preproglucagon processing yields mature 29–AA glucagon plus:
A. GLP-1 and GLP-2
B. Insulin and amylin
C. C-peptide and zinc
D. IRS-1 and SH2

A. GLP-1 and GLP-2

After a high-protein meal, amino acids typically cause glucagon to:
A. Fall below fasting
B. Normalize immediately
C. Remain high or increase
D. Become undetectable

C. Remain high or increase

During fasting-feeding cycles, which hormone varies more?
A. Glucagon
B. Insulin
C. Cortisol
D. Epinephrine

B. Insulin

In a binding assay using intact insulin receptors, the subunit that binds insulin is:
A. β subunit, cytosolic tail
B. α subunit, cytosolic tail
C. α subunit, extracellular domain
D. β subunit, extracellular domain

C. α subunit, extracellular domain

A mutation truncating the receptor’s cytosolic kinase region most directly affects which subunit?
A. β subunit, transmembrane/cytosolic
B. α subunit, extracellular binding
C. α subunit, nuclear translocation
D. β subunit, secreted peptide

A. β subunit, transmembrane/cytosolic

Minutes after insulin binds, the earliest receptor event is:
A. Serine phosphorylation of enzymes
B. cAMP synthesis by adenylate cyclase
C. PIP2 hydrolysis via Gq
D. Tyrosine autophosphorylation of β

D. Tyrosine autophosphorylation of β

In insulin signaling, the principal substrate phosphorylated by the receptor is:
A. CREB
B. IRS-1
C. Phosphodiesterase
D. Phospholamban

B. IRS-1

After IRS-1 phosphorylation, docking occurs through proteins containing:
A. SH2 domains
B. PH domains
C. PDZ domains
D. SH3 domains

A. SH2 domains

A hormone receptor that activates adenylate cyclase to raise cAMP is best classified as:
A. Receptor tyrosine kinase
B. Nuclear transcription receptor
C. GPCR
D. Ligand-gated ion channel

C. GPCR

The glucagon receptor most directly couples to which G-protein?
A. Gi
B. Gs
C. Gq
D. G12/13

B. Gs

In hepatocytes, glucagon binding most directly increases:
A. IP3
B. DAG
C. cGMP
D. cAMP

D. cAMP

cAMP activates PKA by:
A. Dephosphorylating catalytic subunits
B. Phosphorylating regulatory subunits
C. Dissociating regulatory from catalytic
D. Opening membrane calcium channels

C. Dissociating regulatory from catalytic

After activation, PKA phosphorylates key enzymes mainly on:
A. Serine residues
B. Tyrosine residues
C. Threonine residues
D. Cysteine residues

A. Serine residues

The phosphorylated-enzyme message is primarily terminated by:
A. Adenylate cyclase inhibition
B. Gs binding GDP
C. SH2 domain sequestration
D. Protein phosphatases removing phosphate

D. Protein phosphatases removing phosphate

cAMP is rapidly degraded to AMP by:
A. Protein phosphatase 1
B. Membrane phosphodiesterase
C. Phospholipase Cβ
D. Guanylyl cyclase

B. Membrane phosphodiesterase

Caffeine increases cAMP primarily by inhibiting:
A. Protein phosphatases
B. Adenylate cyclase
C. Phosphodiesterase
D. Tyrosine kinase

C. Phosphodiesterase

A methylxanthine’s metabolic effect most closely mimics:
A. Postprandial insulin surge
B. Insulin-induced storage state
C. Low catecholamine tone
D. Fasted glucagon/epinephrine state

D. Fasted glucagon/epinephrine state

A CRE-binding protein directly phosphorylated by PKA is:
A. IRS-1
B. CREB
C. GLUT2
D. KCNJ11

B. CREB

CREs that mediate cAMP-hormone transcriptional effects are located in:
A. Promoter regions of genes
B. Ribosomal RNA operons
C. Mitochondrial DNA control region
D. Lysosomal membrane proteins

A. Promoter regions of genes

Cortisol signaling is best summarized as:
A. GPCR → cAMP → PKA → gene expression
B. RTK → IRS-1 docking → gene expression
C. Gq → PIP2 hydrolysis → gene expression
D. Intracellular receptor binding → nucleus → gene expression

D. Intracellular receptor binding → nucleus → gene expression

Overall, catecholamines primarily cause:
A. Fuel storage predominance
B. Glycogen synthesis predominance
C. Increased fuel mobilization
D. Reduced substrate availability

C. Increased fuel mobilization

β-adrenergic receptors generally signal through:
A. Gq and PLCβ
B. Gs and adenylate cyclase
C. Gi and ion channels
D. JAK-STAT pathway

B. Gs and adenylate cyclase

The major adrenergic receptor in human heart and its primary agonist:
A. β1; norepinephrine
B. β2; norepinephrine
C. β3; epinephrine
D. α1; epinephrine

A. β1; norepinephrine

The adrenergic receptor prominent in liver/muscle fuel mobilization, with epinephrine > norepinephrine potency:
A. β1 receptor
B. α1 receptor
C. β3 receptor
D. β2 receptor

D. β2 receptor

Receptor that mediates vascular/bronchial/uterine smooth muscle contraction:
A. β1 receptor
B. α1 receptor
C. β2 receptor
D. β3 receptor

C. β2 receptor

A candidate “weight-loss” agonist increasing thermogenesis would target:
A. β3 receptor
B. β2 receptor
C. α1 receptor
D. β1 receptor

A. β3 receptor

Increased cardiac contraction with β1 stimulation is partly via PKA phosphorylation of:
A. CREB
B. Phospholamban
C. IRS-1
D. Phosphodiesterase

B. Phospholamban

Only 30–40% of “glucagon” is mature; major extra-pancreatic source of fragments is:
A. Hepatocytes
B. Skeletal myocytes
C. Renal tubule cells
D. Intestinal L cells

D. Intestinal L cells

A patient receives an α1 agonist and develops increased afterload. The primary postsynaptic α1 effect is:
A. Vascular smooth muscle contraction
B. Adipose thermogenesis increase
C. Insulin vesicle exocytosis
D. Bronchial smooth relaxation

A. Vascular smooth muscle contraction

During sympathetic activation, α1 signaling in hepatocytes can directly increase:
A. Glycogen synthesis
B. Glucose uptake
C. Hepatic glycogenolysis
D. Ketone clearance

C. Hepatic glycogenolysis

An α1 receptor couples into the PIP2 system. Which G-protein mediates this pathway?
A. Gi
B. Gq
C. Gs
D. G12/13

B. Gq

In α1 signaling, activation of Gq most directly stimulates:
A. Protein phosphatases
B. Phosphodiesterase
C. Adenylate cyclase
D. Phospholipase Cβ

D. Phospholipase Cβ

A clinic measures waist–hip ratio. A high value most strongly indicates:
A. Brown fat predominance
B. Gluteofemoral fat predominance
C. Visceral periintestinal adipocytes
D. No fat redistribution

C. Visceral periintestinal adipocytes

Visceral periintestinal adipocytes fat distribution pattern is associated with diabetes risk because it correlates with:
A. Reduced insulin sensitivity
B. Increased insulin sensitivity
C. Increased glucagon clearance
D. Reduced catecholamine tone

A. Reduced insulin sensitivity

A patient with uncontrolled diabetes reports polyuria and intense thirst. Which sequence best explains the mechanism described here?
A. ADH excess, water retention, edema
B. Tubular necrosis, oliguria, azotemia
C. SIADH physiology, hyponatremia, coma
D. Osmotic diuresis, dehydration, ↑glucose

D. Osmotic diuresis, dehydration, ↑glucose

A newborn develops diabetes within the first 3 months. The most common permanent form involves an activating KCNJ11 mutation. What is the key functional consequence?
A. KATP closes, Ca2+ blocked
B. GLUT2 fails, ATP drops
C. KATP stays open, Ca2+ blocked
D. Insulin receptor absent, IRS-1 fails

C. KATP stays open, Ca2+ blocked

Chronic hyperglycemia can distort membrane/serum proteins and slow degradation via:
A. Nonenzymatic glycosylation
B. Enzymatic hydroxylation
C. Proteasome hyperactivation
D. Mitochondrial uncoupling

A. Nonenzymatic glycosylation

Which long-term complication cluster best fits microvascular diabetic disease?
A. Coronary stroke PAD
B. Aortic aneurysm dissection
C. Retinopathy nephropathy neuropathy
D. COPD asthma bronchiectasis

C. Retinopathy nephropathy neuropathy

Which complication cluster best fits macrovascular diabetic disease in these notes?
A. Retinopathy, nephropathy, neuropathy
B. Coronary cerebral peripheral disease
C. Dermatitis, urticaria, eczema
D. Myopathy, arthropathy, osteopenia

B. Coronary cerebral peripheral disease

After KATP channel closure in β-cells (by ATP or sulfonylurea), which event most directly triggers insulin vesicle fusion with the membrane?
A. Increased intracellular Ca2+
B. Decreased intracellular cAMP
C. Increased IP3 signaling
D. Reduced ATP:ADP ratio

A. Increased intracellular Ca2+

The pore-forming unit of the β-cell KATP channel is encoded by:
A. HLA
B. KCNJ11
C. ABCC8
D. CREB

B. KCNJ11

The regulatory subunit that binds sulfonylureas is encoded by:
A. ABCC8
B. KCNJ11
C. PEPCK
D. IRS-1

A. ABCC8

Connie has fasting hypoglycemia with inappropriately high insulin; symptoms improve after eating. Most likely diagnosis:
A. Type 1 diabetes
B. Addison disease
C. Insulinoma
D. MODY type 2

C. Insulinoma

Confusion, fatigue, and blurred vision during hypoglycemia are classified as:
A. Osmotic manifestations
B. Cholinergic manifestations
C. Musculoskeletal manifestations
D. Neuroglycopenic manifestations

D. Neuroglycopenic manifestations

Why is C-peptide useful for assessing β-cell function?
A. Secreted only with exogenous insulin
B. Equimolar secretion, slower clearance
C. Rapidly cleared faster than insulin
D. Produced only by α-cells

B. Equimolar secretion, slower clearance

MODY patients can still produce/release insulin, but typically require:
A. Severe hypoglycemia
B. Basal fasting glucose
C. Higher glucose levels
D. Low catecholamines

C. Higher glucose levels

Glucagon can increase PEPCK gene transcription via cAMP. Insulin antagonizes this at gene expression via:
A. CRE in promoter
B. IRE in promoter
C. SH2 docking site
D. PIP2 response element

B. IRE in promoter

Insulin receptor mediates internalization of receptor-bound insulin molecules. This causes what pharmacologic phenomenon?
A. Receptor sensitization
B. Second-messenger amplification
C. Gq coupling switch
D. Receptor downregulation

D. Receptor downregulation