1) INSULIN

INSULINThere are four categories of Diabetes

mellitus :1. Type 1 Diabetes mellitus (insulin-

dependent diabetes)2. Type 2 Diabetes mellitus (non

insulin-dependent diabetes)3. Type 3 Diabetes mellitus (refer to

multiple other spesifik causes of an elevated blood glucose)

4. Type 4 Diabetes mellitus (Gestational diabetes mellitus)

- Insulin is a small protein with a molecular weight in humans of 5808

- Insulin containts 51 amino acids arranged in two chains (A & B) linked by disulfide bridges

- Proinsulin is a long single-chain protein molecule

- Proinsulin is hydrolyzed into insulin and a residual connecting segment called C-peptide by removal of four amino acids

- Proinsulin is processed within the golgi apparatus and packaged into granules

- The entire human pancreas contains up to 8 mg of insulin.

Insulin is bound by specialized receptor that are found on the membrane of most tissues. The receptor name are insulin receptor substrate – 1 and – 2 Glucocorticoid lower the afinty of insulin receptor (IRS-1, IRS-2)

- Insulin is released from pancreatic B cells in response to variety of stimulies

- Several stimulants that involved in insulin secretion : Other sugars (eg.mannose) Certain amino acids (eg, leucine, arginine) Vagal activity

- The mechanism of insulin secretion : In the resting cell with normal ATP levels potassium diffuses down its concentration gradient through ATP- gated potassium channel maintaning the intracellular potential at a fully polarized insulin release is minimal. If glucose concentation rises ATP production increases potassium channel close depolarization of the cell voltage-gated calcium channels open more calcium enter the cell increased intracelluler calcium triggers secretion of the hormone.(Insulin secretagogues groups have same mechanism)

Mechanism of Insulin Secretion

Hyperglycemia(glucose concentration rises)

ATP production

Intracellular ATP levels

ATP-dependent potassium channel Close

Decreased outward potassium efflux

Depolarization of B cells

Opening of Voltage-gated calcium channel

More calcium enter the cells

Intracellular calcium

Triggers secretion of insulin hormone

Commercial insulin preparations differences in :- The recombinant DNA production

techniques- Amino acid sequence- Concentration- Solubility- Time of onset and duration of their

biologic action.

Four principal types of insulins are :1. Rapid-acting with very fast onset and short duration2. Short-acting with rapid onset of action3. Intermediete-acting4. Long-acting with slow onset of action

- Intermediate or long-acting insulins are used to provide basal or background coverage

- Rapid-acting or short insulins are used to meet the mealtime requirements

- Alternative intensive regiment referred to as Multiple Daily Injections (MDI) use long-acting or intermediate-acting insulins with multiple boluses of rapid-acting or short-acting insulin.

1. Rapid-acting insulin- Permit more physiologic prandial insulin replacement.- Duration of action is rarely more than 3 – 5 hours.

2. Short-acting insulin- Soluble crystalline zinc insulin- Its effect appears within 30 minutes and peaks between 2 & 3 hours after subcutaneous injection- The only type that should be administered intravenously- Particularly useful for IV therapy in the management of diabetic ketoacidosis, after surgery or during acute infections- In high concentration : this insulin molecules self agregate in antiparallel fashion form dimers stabilize around zinc ions create insulin hexamers.

3. Intermediate-acting and long-acting insulina. Lente insulinb. NPH (Neutral Protamine Hagedorn, or isophane) insulinc. Ultralente insulind. Insulin glargine

Mechanism of Action of Insulin

Insulin → enzyme dephosphorylation → inhibition of glycogenolysis dan lipolysis

Insulin → pyruvat dehydrogenase enzyme activation → pyruvat oxydation ↑ → pyruvat storage ↓ → glukoneogenesis ↓

a. Portable pen injectorsb. Continuous subcutaneous insulin

infusion devices (CSII, Insulin Pump)c. Inhaled insulin

A. HypoglycemiaB. Insulin allergyC. Immune insulin resistanceD. Lipodystrophy at injection sites

THANK YOU Be A Good Doctor By Making Correct

Prescription