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
- Post-prandial hormones (GLP1, CCK, Ach)
- Glucagon
and inhibited by
- \(\alpha_2\) agonists (i.e. catecholamines)
- Cortisol
- Fasting
- Exercise
- 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