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MSC Unit 7 Insulin Pharmacology 1 & 2 ATTOUB
MSC Unit 7 Insulin Pharmacology 1 & 2 ATTOUB
Insulin Synthesis
Insulin is a peptide hormone composed of 51 amino acids secreted by the pancreatic -cells of Islets of Langerhans y p g Human insulin used in the treatment and control of diabetes mellitus is now produced by a special strain of Escherichia coli that has been genetically altered to contain the gene for human insulin
Insulin Synthesis
Pro-hormone convertases/ Carboxypeptidase Pro-hormone convertases/ P h t / Carboxypeptidase
Pro-Insulin
Insulin
Insulin is synthesized as a pro-hormone, pro-insulin, that undergoes proteolytic cleavage to form insulin and peptide C Mature insulin is composed of two polypeptide chains (- and chain), chain) connected by disulfide bonds The entire human pancreas bonds. contains up to 8 mg of insulin Circulating C-peptide has no known biological function but serves as a better index of insulin secretion
Insulin Secretion
Insulin secretion is a tightly regulated process designed to provide stable concentrations of glucose in blood during both fasting and g g g feeding. This regulation is achieved by the coordinated interplay of various nutrients, gastrointestinal hormones, pancreatic hormones, and autonomic neurotransmitters Glucose is the principal stimulus to insulin secretion in human human. Glucose enters cell by facilitated transport via Glut 2 transporter gg The rise in intracellular Ca2+ triggers insulin secretion When evoked by glucose, insulin secretion is biphasic: The first phase reaches a peak after 1 to 2 minutes and is short-lived; the second phase has a delayed onset but a longer duration. These phases represents release of insulin stored in granules and newly synthesized insulin, respectively
Release of insulin
Diabetes Mellitus
Diabetes mellitus is defined as hyperglycemia due to absolute or relative lack of insulin with various degrees of insulin resistance. By 2010, the number of diabetes persons is expected to approach 220 million The most common forms are type 1 diabetes, with absolute lack of insulin, and type 2 diabetes which is due to the combination of insulin resistance and insufficient insulin secretion A large number of individuals are asymptomatic and do not know they have the disease The chronic hyperglycemia of diabetes is associated with long-term g , y , g , p y damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels
Type 1 Diabetes
Insulin Dependent Diabetes Mellitus (IDDM) or Type 1 Diabetes, or juvenile diabetes: results from a destruction of insulin-secreting -cells by ll b an autoimmune mechanism d i a period of several i h i during i d f l years leading to absolute insulin deficiency Loss of -cells may be due to: - Antibodies against -cell proteins (glutamic acid decarboxylase, g p (g y , tyrosine phosphatase IA-2, insulin) - Viral infection -A i Actions of chemical toxins f h i l i ~ 10% of all patients yp y q Type 1 diabetes always requires treatment with insulin to maintain blood glucose concentrations close to normal
Type 2 Diabetes
Non-Insulin Dependent Diabetes Mellitus (NIDDM) or Type 2 Diabetes: is a frequent consequence of the metabolic syndrome (obesity, insulin resistance, dyslipidemia, hypertension) ~ 90% of all patients Type 2 DM with larger genetic component than type 1 is increasing DM, 1, in frequency. The genetic basis for type 2 DM cannot change in such a short time; thus, other contributing factors, including increasing age, obesity, sedentary lifestyle, and low birth weight, must account for this dramatic increase. In addition, type 2 DM is being diagnosed with remarkable frequency in preadolescents and adolescents Type 2 diabetes is characterized by tissue resistance to the action of insulin combined with a relative deficiency in insulin secretion
Rapid-acting and short-acting insulins are often administered two to three times a day or more
Pharmakokinetic characteristics of the most commonly used insulin preparations and analogs