Q4 LONG ANSWER 10M ★ High-yield

Describe the sources and fates of blood glucose. Explain the hormonal regulation of blood glucose in the fed and fasting states.

Biochemistry · 1st Professional — Pre-Clinical

Normal Values

State	Plasma glucose
Fasting	70–100 mg/dL
2 hours post-prandial	< 140 mg/dL
Random	80–140 mg/dL
Renal threshold	180 mg/dL
Hypoglycaemia	< 70 mg/dL; symptoms below 55

Blood glucose is held within narrow limits because the brain and RBC depend on it absolutely

Sources and Fates of Blood Glucose

Sources (raise glucose)	Fates (lower glucose)
Dietary carbohydrate	Oxidation by tissues (glycolysis → TCA)
Glycogenolysis (liver)	Glycogenesis (liver, muscle)
Gluconeogenesis (liver, kidney)	Lipogenesis — conversion to fat
—	HMP shunt — NADPH and ribose
—	Excretion in urine above the renal threshold

Hormonal Regulation

A. Insulin — the only hypoglycaemic hormone

Secreted by β cells in response to a rise in blood glucose
↑ Glucose uptake by GLUT-4 in muscle and adipose tissue
↑ Glycogenesis; ↓ glycogenolysis
↓ Gluconeogenesis (represses PEPCK)
↑ Glycolysis (induces glucokinase, PFK, pyruvate kinase)
↑ Lipogenesis; ↓ lipolysis and ketogenesis

B. The counter-regulatory hormones

Hormone	Chief action	Speed
Glucagon	↑ Hepatic glycogenolysis and gluconeogenesis; the first line of defence	Minutes
Adrenaline	↑ Glycogenolysis in liver and muscle; ↓ insulin release (α2)	Seconds
Cortisol	↑ Gluconeogenesis (induces PEPCK); ↓ peripheral uptake; ↑ proteolysis	Hours
Growth hormone	↓ Peripheral glucose uptake; ↑ lipolysis	Hours
Thyroxine	↑ Absorption and glycogenolysis	Days

CLINICAL PEARL

Note the asymmetry: only one hormone lowers blood glucose, but four raise it. Hypoglycaemia kills within minutes; hyperglycaemia takes years. The body defends accordingly.

Response in the Fed State

Meal → ↑ Blood glucose → ↑ Insulin, ↓ glucagon → Liver: ↑ glycogenesis, ↑ glycolysis, ↑ lipogenesis → Muscle: ↑ GLUT-4 → ↑ uptake and glycogen → Adipose: ↑ uptake, ↑ triglyceride synthesis → Blood glucose returns to normal in 2 hours

Response in Fasting and Starvation

Phase	Time	Chief source of glucose
Fed	0–4 h	Dietary
Post-absorptive	4–16 h	Hepatic glycogenolysis
Early fasting	16–48 h	Glycogen exhausted → gluconeogenesis
Prolonged starvation	> 48 h – weeks	Gluconeogenesis (from muscle protein) + ketone bodies spare glucose

Liver glycogen (about 100 g) lasts only 18–24 hours
Muscle glycogen cannot raise blood glucose — muscle lacks glucose-6-phosphatase; it can only be used locally, or exported as lactate for the Cori cycle
In prolonged starvation the brain adapts to use ketone bodies, which spares protein and prolongs survival

Glucose Tolerance Test

75 g oral glucose after an overnight fast; samples at 0 and 2 hours
Normal — fasting < 100, 2 h < 140 mg/dL
Impaired glucose tolerance — 2 h between 140 and 199
Diabetes — fasting ≥ 126 or 2 h ≥ 200 mg/dL
Lag storage curve — a high peak with rapid fall; seen after gastrectomy and in hyperthyroidism

Applied Aspects

Diabetes mellitus — insulin deficiency or resistance → the cells are "starving in the midst of plenty"; unrestrained gluconeogenesis and lipolysis
Hypoglycaemia — commonest cause is insulin or sulfonylurea therapy. Also insulinoma, alcohol, Addison disease, liver failure
Whipple triad confirms true hypoglycaemia — symptoms, a low measured glucose, and relief on giving glucose
HbA1c reflects the average glucose over 8–12 weeks — the standard measure of long-term control
Dawn phenomenon — early-morning hyperglycaemia from the nocturnal surge of growth hormone and cortisol
Somogyi effect — nocturnal hypoglycaemia provokes a counter-regulatory surge and rebound morning hyperglycaemia; treated by reducing, not increasing, the evening insulin
Glycosuria appears above the renal threshold of 180 mg/dL; in pregnancy the threshold falls, giving benign glycosuria

All questions in Carbohydrate Metabolism I: Glycolysis, TCA & Gluconeogenesis

Every Biochemistry chapter →