Control of blood glucose

Vivian Imbriotis | April 11, 2026

BGL is tightly regulated. Fasting BGL ~ 5mM, post prandial BSL ~ 10mM.

Glucose flux consists of

  • Absorption of carbohydrates
  • Consumption by glycolysis
  • Storage and release from glycogen stores
  • Gluconeogenesis (80% liver, 20% kidney)

Insulin and glucagon release regulates blood glucose.

The primary effector is the liver, which functions as a glucostat.

Response to hyperglycaemia

  • Insulin released \(\uparrow BSL \to \uparrow ATP \to K_{ATP}\) blockade, glucagon suppressed
  • Liver: increased glycolysis, glycogenesis; decreased gluconeogenesis, free fatty acid oxidation (ketone production)
  • GLUT-4 bearing tissues (muscle, adipose): increased glycolysis, glycogenolysis

Response to hypoglycaemia

  • Insulin suppressed, glucagon released, catecholamines released
  • Liver: increased glycogenolysis, gluconeogenesis, FFA oxidation (ketone production); decreased glycolysis, glycogenesis

Insulin is a polypeptide anabolic hormone produced in the \(\beta\) cells of the pancreatic islets. C-peptide is produced as a byproduct of its production. It is stored in intracellular vesicles.


Insulin release

Glucose is principal stimulus. Beta cell ATP acts as a measure of serum glucose concentration

$$\uparrow BGL \xrightarrow{GLUT-2} \text{Glucose}_{\beta \text{ cell}} \xrightarrow{glucokinase} \text{G6P} \to \text{pyruvate} + 2ATP \to \text{citric acid cycle} \to \uparrow[ATP]_{\beta \text{ cell}} $$

The \(K_{ATP}\) channel is blocked in the presence of ATP, and causes membrane voltage to rise until...

$$\uparrow[ATP]_{\beta \text{ cell}} \to K_{ATP} \text{ blockade} \to \text{depolarization}$$

Calcium binds to calmodulin which effects exocytosis of insulin-filled vesicles

$$\uparrow[Ca]_{\beta \text{ cell}} \to \text{exocytosis}$$

Other substrates that raise \(\uparrow[ATP]_{\beta \text{ cell}}\) also cause insulin release (amino acids, keto acids, fatty acids).

Insulin release is potentiated by

  1. Post-prandial hormones (GLP1, CCK, Ach)
  2. Glucagon

and inhibited by

  1. \(\alpha_2\) agonists (i.e. catecholamines)
  2. Cortisol
  3. Fasting
  4. Exercise
  5. Somatostatin


Insulin effects

Binds to insulin receptor; receptor-ligand complex endocytosed and destroyed. Activates PI3k second messenger pathway.

In GLUT-4 bearing tissues (adipose, skeletal muscle)

  • Translocate GLUT-4 vesicles to surface \(\to\) glucose absorption \(\to\ \ \downarrow\) BGL
  • Increase lipoprotein lipase + free fatty acid transporters on adipose tissues \(\to\) absorbtion of triglyceride and free fatty acids

In the liver

  • \(\uparrow\) Glucokinase - increased glycogenesis
  • \(\downarrow\) G-6-phosphatase - decreased gluconeogenesis
  • \(\downarrow\) free fatty acid oxidation \(\to \ \downarrow\)ketone production

In the heart

  • \(\uparrow [Ca^{2+}]_{intracellular} \to \uparrow \text{inotropy} \ (\beta_1 \text{ independent})\)

In all cells

  • Intracellular shift of potassium and phosphate


Insulin is a polypeptide catabolic hormone produced in the \(\alpha\) cells of the pancreatic islets. The mechanics of glucagon release are unclear.

Inhibitiors

  • Insulin
  • Hyperglycaemia, partly by means of increased insulin secretion
  • Post-prandial hormones (e.g. GLP-1)

Stimulation of glucagon secretion:

  • Hypoglycaemia (direct stimulus and loss of insulin-mediated inhibition)
  • Amino acids
  • Fasting
  • Exercise
  • \(\alpha_2\) agonists (i.e. catecholamines)

Effects:

  • Increased gluconeogenesis
  • Increased glycogenolysis
  • Increased free fatty acid oxidation \(\to \ \uparrow)ketone production
  • Decreased hepatic glycogenesis
  • \(\uparrow [Ca^{2+}]_{cardiomyocyte} \to \uparrow \text{inotropy} \ (\beta_1 \text{ independent})\)