A 45-year-old man with type 2 diabetes mellitus is brought to the emergency department in a hypoglycaemic coma (blood glucose 32 mg/dL). His wife reports he took his usual insulin dose but skipped dinner. IV access is difficult to establish due to severe dehydration. The hormone marked **B** in the diagram is administered as 1 mg intramuscularly. Which of the following best explains why this intervention is effective in this acute setting but would likely FAIL in a chronic alcoholic with similar hypoglycaemia?

Explanation

## Why "The hormone marked B mobilizes hepatic glycogen stores, which are depleted in chronic alcoholics due to cirrhosis and reduced glycogen synthesis" is right The hormone marked **B** is glucagon, secreted by pancreatic α cells in response to hypoglycaemia. Its PRIMARY TARGET is the liver, where it stimulates glycogenolysis (rapid mobilization of hepatic glycogen, which normally sustains blood glucose for 12–24 hours). In the acute hypoglycaemic diabetic patient with normal hepatic glycogen stores, glucagon rapidly restores blood glucose by breaking down glycogen. However, in chronic alcoholics, hepatic glycogen is chronically depleted due to: (1) impaired glycogen synthesis from chronic ethanol metabolism and malnutrition, (2) cirrhosis and hepatocellular damage reducing hepatic reserve, and (3) prolonged fasting/malnutrition. When hepatic glycogen is absent, glucagon cannot mobilize glucose and is therefore ineffective—there is "nothing to mobilize." This is a classic teaching point in emergency medicine and endocrinology: glucagon fails in states of hepatic glycogen depletion (Guyton & Hall 14e Ch 79; KD Tripathi 9e Ch 19). ## Why each distractor is wrong - **"The hormone marked B acts on muscle to increase glucose uptake, which is impaired in alcoholics due to myopathy"**: Glucagon has NO effect on muscle—muscle lacks glucagon receptors. Glucagon is catabolic and mobilizes fuel from liver and adipose, not muscle. This is a fundamental pharmacological principle. - **"The hormone marked B stimulates pancreatic β cells to secrete insulin, a mechanism lost in type 1 diabetes"**: Glucagon does not stimulate insulin secretion; it is a counter-regulatory hormone that opposes insulin. Moreover, the question stem specifies a type 2 diabetic, not type 1, and the mechanism of glucagon failure in alcoholics is hepatic glycogen depletion, not β-cell dysfunction. - **"The hormone marked B increases renal glucose reabsorption, which is impaired in alcoholics with diabetic nephropathy"**: Glucagon does not act on the kidney to increase glucose reabsorption. Its targets are liver (glycogenolysis, gluconeogenesis, ketogenesis) and adipose (lipolysis). Renal glucose handling is not a glucagon action. **High-Yield:** Glucagon is ineffective in hypoglycaemia when hepatic glycogen is depleted (chronic alcoholism, prolonged fasting, type 1 DM with poor control)—in these cases, use IV dextrose instead. [cite: Guyton & Hall 14e Ch 79; KD Tripathi 9e Ch 19]