Antidiabetic drugs - Insulin

How is insulin produced?

By beta cells of the pancreas in response to changes in blood glucose

What is insulin?

A polypeptide with 51 amino acids arranged in two chains (A and B) linked by a disulphide bridge

How is rapid acting insulin made?

As human insulin analogs made through recombinant DNA techniques

What are the rapid acting insulins?

Insulin Lispro, Insulin Aspart, and Insulin Glulisine

What is the onset of action of Insulin Lispro after subcutaneous injection?

15-30 minutes

What is the onset of action of Insulin Aspart after subcutaneous injection?

10-20 minutes

What is the onset of action of Insulin Glulisine after subcutaneous injection?

20-30 minutes

What is the duration of action of Insulin Lispro?

3-5 hours

What is the duration of action of Insulin Aspart?

3-5 hours

What is the duration of action of Insulin Glulisine?

1-2.5 hours

How does inhaled insulin work?

Human insulin is absorbed onto carrier particles

What is Afrezza?

Breath powered insulin inhaler

What patients would Afrezza be contraindicated in?

Patients with respiratory issues

What is the speed of onset after Afrezza is inhaled?

10-15 minutes

How does short acting insulin differ from rapid acting insulin?

Short acting insulin has a slower onset and a longer duration of action

What is the available short acting insulin?

Insulin Regular

What is the onset of action of Insulin Regular after subcutaneous injection?

30-60 minutes

What is the duration of action of Insulin Regular?

5-8 hours

What is the available intermediate acting insulin?

Insulin NPH- Neutral Protamine Hagedorn aka Isophane

What does Insulin NPH aka Isophane contain?

Insulin and protamine

What is the onset of action of Insulin NPH aka Isophane after subcutaneous injection?

1-2 hours

What is the duration of action of Insulin NPH aka Isophane?

18-24 hours

What are the available long acting insulins?

Insulin Glargine, Insulin Detemir, and Insulin Degludec

What is the onset of action of Insulin Glargine after subcutaneous injection?

1-1.5 hours

What is the onset of action of Insulin Demetir after subcutaneous injection?

1-2 hours

What is the onset of action of Insulin Degludec after subcutaneous injection?

1-2 hours

What is the duration of action of Insulin Glargine?

20-24 hours

What is the duration of action of Insulin Demetir?

>24 hours

What is the duration of action of Insulin Degludec?

>24 hours

How are insulins categorized?

By differences in onset, peak, duration, concentration, and route of delivery

What is onset?

How quickly medications work

What is an insulin peak?

How long it takes to achieve maximum impact

What is duration?

How long it takes before a medication wears off

How are rapid or short acting insulins used?

To correct the transient prandial hyperglycemia associated with meals

How are intermediate or long acting insulins used?

To provide basal insulin levels

What is the general function of insulin?

Activate insulin receptors to reduce circulating glucose

What kind of receptors are insulin receptors?

Receptors of the tyrosine kinase receptor family

Where are insulin receptors located in the cell?

Plasma membrane

What are the primary target cells with insulin receptors?

Cells of the liver, skeletal muscle, and adipose tissue

What is the result of insulin receptor activation?

Leads to tyrosine phosphorylation of receptor substrate proteins, phosphorylated proteins then alter the synthesis or activity of enzymes involved in the metabolic processes

How does tyrosine kinase activation through insulin receptor activation impact glucose transporters?

Increases the insertion of GLUT-4 subtype transporters into cell membranes of skeletal muscle and adipose tissue

What is the impact of increased GLUT-4 insertion in cell membranes of skeletal muscle and adipose tissue?

Enables increased glucose uptake into cells

How are metabolic processes impacted by insulin receptor activation?

Glycogen synthase activity and glycogen formation increases, protein synthesis increases, and lipolysis decreases

What is the action of insulin on the liver?

Decreases gluconeogenesis, decreases glycogenolysis, decreases proteolysis, increases glycogenesis, and increases lipogenesis

What is the action of insulin on skeletal muscle?

Increases glucose uptake, increases glycogenesis, increases amino acid uptake, and increases protein synthesis

What is the action of insulin on adipose tissue?

Increases the conversion of glucose to fatty acids for storage as triglyceride

Why is insulin usually given as an injection, usually subcutaneously?

Insulin is destroyed in the GI tract

How is insulin inactivated and excreted?

Insulin is inactivated in the liver and excreted by the kidney

What percent of administered insulin is excreted unchanged?

10%

How can insulin be administered in critical clinical situations?

Via IV of IP infusion

What are the therapeutic uses of insulin?

Management of type 2 diabetes not controlled by diet and oral antidiabetic agents and type 1 diabetes

What are the adverse effects of insulin?

Hypoglycemia, weight gain, insulin allergy, and lipodystrophy

What is the most common adverse effect of insulin?

Hypoglycemia

What is the rare adverse effect of insulin?

Lipodystrophy, which is atrophy of subcutaneous tissue at injection site