Clinical Uses of Insulin

Clinical Uses of Insulin

• Patients with DM1 require long-term maintenance treatment with insulin.
• An intermediate-acting preparation is often combined with a short-acting preparation taken before meals.
• Soluble insulin is used (i.v.) in emergency treatment of hyperglycemic diabetic emergencies (ketoacidosis).
• Many patients with DM2 ultimately require insulin treatment.
• Short-term treatment of patients with DM2 or impaired glucose tolerance during intercurrent events (operations, infections, myocardial infarction).

Adverse Effects of Insulin

• Hypoglycemia: the most common complication resulting from excessive insulin effect.
• Insulin-induced immunological complications: the most common form is the formation of Abs to insulin or to non-insulin protein content.
• Hypokalemia: may occur in acidosis patients who use a lot of insulin and glucose, leading to patient death with abnormal heart beat.
• Weight gain: due to increased caloric storage of glucose by insulin and some is due to renal sodium retention resulting in fluid retention and edema.

Pancreatic Islet Cells and Their Secretory Products

• Alpha cells secrete glucagon, which opposes many actions of insulin by increasing blood glucose through activation of hepatic glycogenolysis and gluconeogenesis.
• Beta cells secrete insulin, the storage and anabolic hormone of the body, and amylin, which modulates appetite, gastric emptying, and glucagon and insulin secretion.
• Delta cells secrete somatostatin, a universal inhibitor of secretory cells.
• PP cells secrete pancreatic polypeptide (PP), a small protein that facilitates digestive processes.

Diabetes Mellitus

• A chronic metabolic disorder characterized by a high blood glucose concentration (fasting plasma glucose > 7.0 mmol/l, or plasma glucose > 11.1 mmol/l 2 hours after a meal).
• Caused by insulin deficiency, often combined with insulin resistance.

Types of Diabetes Mellitus

• Type 1: Insulin-dependent diabetes mellitus (IDDM), resulting from the destruction of pancreatic beta cells due to an autoimmune process.
• Type 2: Non-insulin dependent diabetes mellitus (NIDDM), resulting from a combination of insulin resistance and altered insulin secretion.
• Gestational diabetes: glucose intolerance during pregnancy.

Treatment of DM Type 1

• Therapy involves dietary instruction, parenteral insulin (to maintain control of basal and postprandial glucose level, avoid ketoacidosis, and maintain acceptable level of glycosylated Hb (Hb A1c)).
• Careful attention by the patient to factors that change insulin requirements: exercise, infections, other forms of stress, and deviation from regular diet.

Treatment of Type 2 DM

• Weight reduction and dietary control.
• Monotherapy with metformin, a 2nd generation sulfonylureas.
• After 5 years, secondary failure is common. Non-insulin antidiabetics are being used in combination with each other or with insulin to achieve better glycemic control.

Insulin Chemistry

• Insulin is a small protein containing 51 amino acids arranged in two chains (A and B) linked by disulfide bridges.
• Proinsulin, a long single-chain protein molecule, is hydrolyzed into insulin and a residual connecting segment called C-peptide by removal of four amino acids.

Insulin Synthesis

• Proinsulin is converted to insulin and C-peptide.

Insulin Secretion

• Insulin is released from pancreatic B cells in response to a variety of stimuli, especially glucose.
• Hyperglycemia results in increased intracellular ATP levels, which close the ATP-dependent potassium channels, resulting in depolarization of the B cell and opening of voltage-gated calcium channels.

Effects of Insulin

• Decreased gluconeogenesis, glycogenolysis, and protein breakdown.
• Increased glycolysis, glycogenesis, lipogenesis, and glucose uptake in skeletal muscle and adipose tissues.