A 24-year-old man presents for an annual check-up. He is a bodybuilder and tells you he is on a protein-rich diet that only allows for minimal carbohydrate intake. His friend suggests he try exogenous glucagon to help him lose some excess weight before an upcoming competition. Which of the following effects of glucagon is he attempting to exploit?

Increased lipolysis in adipose tissues

Increased glucose utilization by tissues

Decreased blood cholesterol level

Increased hepatic gluconeogenesis

Increased hepatic glycogenolysis

A 16-year-old girl is brought to the emergency department unresponsive. A witness reports that she became anxious, lightheaded, and began sweating and trembling a few minutes before she lost consciousness. Her vitals are as follows: blood pressure 95/60 mm Hg, heart rate 110/min, respiratory rate 21/min, and temperature 35.5°C (95.5°F). She becomes responsive but is still somnolent. She complains of dizziness and weakness. A more detailed history reveals that she has drastically restricted her diet to lose weight for the past 18 hours, and has not eaten today. Her skin is pale, wet, and cold. The rest of the physical examination is unremarkable. Blood testing shows a plasma glucose level of 2.8 mmol/L (50.5 mg/dL). Which of the following statements is true?

Hypoglycemia in this patient is being compensated with an increased glycogenolysis rate.

Epinephrine-induced gluconeogenesis is the main process that allows for the compensation of a decreased glucose level.

There is an increase in the glycogen synthesis rate in this patient’s hepatocytes.

The patient’s symptoms are most likely the consequence of increased insulin secretion from the pancreatic islets.

The patient’s hypoglycemia inhibits glucagon release from pancreatic alpha cells.

You have been asked to deliver a lecture to medical students about the effects of various body hormones and neurotransmitters on the metabolism of glucose. Which of the following statements best describes the effects of sympathetic stimulation on glucose metabolism?

Epinephrine increases liver glycogenolysis.

Norepinephrine causes increased glucose absorption within the intestines.

Without epinephrine, insulin cannot act on the liver.

Peripheral tissues require epinephrine to take up glucose.

Sympathetic stimulation to alpha receptors of the pancreas increases insulin release.

Certain glucose transporters that are expressed predominantly on skeletal muscle cells and adipocytes are unique compared to those transporters found on other cell types within the body. Without directly affecting glucose transport in other cell types, which of the following would be most likely to selectively increase glucose uptake in skeletal muscle cells and adipocytes?

Increased levels of circulating insulin

Increased plasma glucose concentration

It is physiologically impossible to selectively increase glucose uptake in specific cells

Decreased plasma glucose concentration

Decreased levels of circulating insulin

A 38-year-old female presents to her primary care physician with complaints of several episodes of palpitations accompanied by panic attacks over the last month. She also is concerned about many instances over the past few weeks where food has been getting stuck in her throat and she has had trouble swallowing. She denies any prior medical problems and reports a family history of cancer in her mother and maternal grandfather but cannot recall any details regarding the type of cancer(s) or age of diagnosis. Her vital signs at today's visit are as follows: T 37.6 deg C, HR 106, BP 158/104, RR 16, SpO2 97%. Physical examination is significant for a nodule on the anterior portion of the neck that moves with swallowing, accompanied by mild lymphadenopathy. A preliminary work-up is initiated, which shows hypercalcemia, elevated baseline calcitonin, and an inappropriately elevated PTH level. Diagnostic imaging shows bilateral adrenal lesions on an MRI of the abdomen/pelvis. Which of the following is the most likely diagnosis in this patient?

Multiple endocrine neoplasia (MEN) IIa

Familial medullary thyroid cancer (FMTC)

Multiple endocrine neoplasia (MEN) I

Multiple endocrine neoplasia (MEN) IIb

Pancreatic endocrine function for USMLE Step 2 CK: High-Yield Physiology Lessons

Islet Anatomy - The Cellular Collective

The Islets of Langerhans are clusters of endocrine cells that act as a coordinated "micro-organ" to regulate blood glucose. Their cellular arrangement is key to their function.

Islet of Langerhans cell types and relative locations

Cell Type	Hormone(s)	Location in Islet	Primary Function
α (Alpha)	Glucagon	Periphery	↑ Blood glucose
β (Beta)	Insulin, Amylin	Center	↓ Blood glucose
δ (Delta)	Somatostatin	Interspersed	Inhibits α & β cells
PP (F cell)	Pancreatic Polypeptide	Periphery	↓ Exocrine secretion

Insulin Synthesis & Release - The Glucose Gatekeeper

Synthesis (in β-cells):
- Preproinsulin synthesized in RER, signal peptide cleaved.
- → Proinsulin folded & disulfide bonds formed in Golgi.
- → Cleaved into Insulin and C-peptide, stored in secretory granules.

Glucose-stimulated insulin release from pancreatic β-cell

Glucose-Stimulated Secretion:

⭐ Exam Favorite: Endogenous insulin release produces equimolar amounts of insulin and C-peptide. Measuring C-peptide can differentiate between endogenous insulin production (e.g., insulinoma) and exogenous insulin administration.

Glucagon & Friends - The Counter-Attack Crew

Secreted by pancreatic α-cells, glucagon is the primary counter-regulatory hormone to insulin.

Triggers:
- Hypoglycemia (primary stimulus, glucose < 70 mg/dL)
- Amino acids (e.g., arginine)
- Sympathetic stimulation (β-adrenergic)
Actions (Liver-centric):
- ↑ Glycogenolysis (rapid effect)
- ↑ Gluconeogenesis (slower, sustained effect)
- ↑ Ketogenesis
Other Players:
- Somatostatin (δ-cells): Universal inhibitor; ↓ insulin & glucagon release.
- Amylin (β-cells): Co-secreted with insulin; ↓ glucagon secretion.

⭐ Glucagonoma: A rare tumor of α-cells, presents with necrolytic migratory erythema, diabetes, and weight loss.

Glucagon signaling pathway and glucose regulation

Pancreatic Pathophysiology - When Sweet Goes Sour

Feature	Type 1 DM	Type 2 DM
Onset	< 30 years	> 40 years
Pathophysiology	Autoimmune β-cell destruction	Insulin resistance, β-cell dysfunction
Genetics	HLA-DR3 & DR4 association	Strong polygenic predisposition
Insulin Level	↓↓	Normal/↑ → ↓
Ketoacidosis	Common	Rare
Histology	Islet leukocytic infiltrate	Islet amyloid polypeptide (IAPP) deposits

-   *Whipple's Triad:* ↓ plasma glucose, neuroglycopenic symptoms (e.g., confusion, anxiety), and symptom resolution with glucose administration.

Glucagonoma: Tumor of α-cells.
- 📌 4 D's: Dermatitis (necrolytic migratory erythema), Diabetes, DVT, Depression.

⭐ Exam Favorite: Autoantibodies against glutamic acid decarboxylase (anti-GAD65) are a key marker for Type 1 Diabetes and can be detected years before clinical onset.

High‑Yield Points - ⚡ Biggest Takeaways

Insulin, from β-cells, drives glucose into muscle and adipose tissue via GLUT4.

Glucagon, from α-cells, counters by promoting hepatic glycogenolysis and gluconeogenesis.

C-peptide is co-secreted with insulin, making it a key marker of endogenous insulin production.

Somatostatin from δ-cells acts as a universal inhibitor of pancreatic endocrine secretion.

Glucose is the primary physiological stimulus for insulin release from β-cells.

Sulfonylureas and meglitinides close the ATP-sensitive K+ channel to trigger insulin secretion.

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