Insulina

Insulin binds to the insulin receptor (RTK), activating intracellular signaling pathways such as PI3K/Akt and MAPK.

• Receptor binding: Insulin binds to the alpha subunit of the insulin receptor, inducing autophosphorylation of the beta subunit.
• PI3K/Akt signaling: Activates PI3K, generating PIP3, which recruits and activates Akt. Akt promotes GLUT4 translocation to the cell membrane, increasing glucose uptake.
• Inhibition of gluconeogenesis: Akt phosphorylates and activates PDE3B, reducing cAMP and decreasing expression of gluconeogenic enzymes such as PEPCK and G6Pase.
• Promotion of storage: Stimulates glycogenesis (activation of glycogen synthase) and lipogenesis (increased fatty acid synthesis).

• Type 1 diabetes: Essential hormone replacement therapy for patients with absolute insulin deficiency.
• Type 2 diabetes: Used when oral agents fail to achieve adequate glycemic control, especially in advanced stages.
• Gestational diabetes: Blood glucose control during pregnancy when diet is insufficient.
• Diabetic ketoacidosis: Intravenous administration to correct severe hyperglycemia and metabolic acidosis.
• Hospital hyperglycemia: Management of blood glucose in critically ill or surgical patients.

Insulin lowers blood glucose by promoting cellular uptake and storage. It also inhibits hepatic glucose production and stimulates protein and lipid synthesis. Common adverse effects include hypoglycemia (dangerous if untreated), weight gain, lipodystrophy at injection sites, and local allergic reactions. Improper use can lead to severe hypoglycemia, coma, and death.

Insulin is contraindicated during hypoglycemic episodes. Dose adjustment is required in renal or hepatic impairment, during pregnancy and lactation, and in the elderly. Frequent glucose monitoring is essential. Patients must be educated on recognizing and managing hypoglycemia. Interactions with other drugs (e.g., beta-blockers, corticosteroids) may alter glycemic control. Insulin should not be mixed with other insulins without consulting the manufacturer.

Approved by the FDA in 1939 (regular insulin). Modern analogs (lispro, aspart, glargine, etc.) were approved between 1996 and 2015. Approved by EMA and global regulatory agencies. Listed as an essential medicine by the WHO.

Dosing is highly individualized. In type 1 diabetes, typically 0.5-1.0 U/kg/day in multiple doses (basal and prandial). In type 2 diabetes, start with 0.1-0.2 U/kg/day and titrate based on blood glucose. Rapid-acting insulins are given 15 minutes before meals; basal insulins once daily. Adjust based on glucose monitoring and HbA1c.

Unopened insulin vials and cartridges should be stored in the refrigerator (2-8°C), do not freeze. Once opened, they can be kept at room temperature (<30°C) for up to 28 days, protected from light and extreme heat. Do not use if the liquid is cloudy or has particles (except NPH insulins which are naturally milky).