class insulin 2
DESCRIPTION
TRANSCRIPT
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INSULIN -1
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
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Pancreas
Exocrine, enzymatic Acinar cells�Endocrine, hormonal-ISLET OF LANGERHANS Alpha cells- Glucagon Beta cells -Insulin, proinsulin, amylin� Delta cells -Somatostatin, � F cells- pancreatic polypeptide
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Endocrine functions of the pancreas
Regulation of storage and use of carbohydrates, �fats and protein within liver, muscle and adipose tissue
Facilitation of cellular storage of nutrients �following a meal
Release of metabolic substrates during fasting�
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ISLET OF LANGERHANS-paracrine regulation
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Insulin-Synthesis and metabolism
Synthesized as a preproinsulin� After cleavage of � signal sequence proinsulin folds and forms S-S bonds In proinsulin A and B chains are � connected by a C peptide Cleavage of C peptide forms� final product Species differences: biologic activities� overlap but antigenic activities don’t
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Synthesis of insulin
Chromosome no-11 Involves all steps of protein synthesis.The signal sequence attaches mRNA to REM. Endopeptidase breaks down the prepro-Ipro-II Secretory vesicles- Insulin+c peptide+ endopeptidase+Zn.
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Release of insulin
GLUT-2 present on ß cells,liver, intestine, kidney-facilitated transportation.(B CELL LIKES GLUT2)
GlucoseG -6-Po4glycolysis pathwaypyruvic acid TCA cycleATP synthesis.
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Release of Insulin
ATP decreases ADP levelsclosing of ATP dependent K channels K inside cell-60mvolts -50mvactivation of voltage dependent Ca channels intracellular Cavesicles move towards membranerelease of insulin.
Meglitinides
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Insulin
Polypeptide consisting of an A and B chain of 21 and 30 aa Two chains are linked by a pair of S-S bonds� An intrachain S-S bond connects 6th and 11th aa �
within A chain Forms a dimer with 2 Zn ions� Hexameric form
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Mechanism of insulin
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Pharmacological actions
RAPID EFFECT
Promotes the uptake & storage of glucose,fats, & protein-effects on liver,muscles and adipose tissue
Carbohydrate Metb lipid metabolism
Protein metabolism
LONG TERM EFFECT
Gene transcription Cell proliferation
and differenciation Protein synthesis Growth regulation
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Effect on Carbohydrate Metabolism
Promotes Muscle Glucose Uptake and Metabolism Storage of Glycogen in Muscle Promotes Liver Uptake, Storage and Use of Glucose
Mechanisms: inactivates liver phosphorylase causes enhanced uptake of glucose from the blood
by the liver cells -by increasing the activity of the enzyme glucokinase
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Effect on Fat Metabolism
Insulin promotes Fat Synthesis and Storage
Synthesis- Insulin promotes glucose transport through the cell membrane into the fat cells
Storage -Adipose Cells-Insulin inhibits the action of hormone-sensitive lipase
Insulin deficiency causes increase metabolic use of fat causing lipolysis of storage fat and release of free fatty acids increase plasma cholesterol and phospholipid excess usage of fats during insulin lack causes ketosis and acidosis
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Effect on Protein Metabolism
insulin promotes protein synthesis and storage stimulates transport of amino acids into the cells
(valine, leucine, isoleucine, tyrosine, phenylalanine) increases the translation of messenger RNA, forming
new proteins increases the rate of transcription of DNA genetic
sequences in cell nuclei inhibits catabolism of proteins depresses the rate of gluconeogenesis
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Type 1 Diabetes:
Impaired or absent ß cell function: insulin secretion
The insulin deficiency results in unacceptable blood glucose control
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Type 2 Diabetes:
Impaired ß cell function: insulin secretion
Impaired insulin action: insulin resistance
Results in unacceptable blood glucose control
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Type 1 & 2 Diabetes:
Minimizing the complications of diabetes requires: Early diagnosis and treatment of diabetes Maintaining HbA1C level < 7%
Achieving HbA1C < 7% requires control of post-prandial and fasting hyperglycemia
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Type 3 DM
Chronic pancreatitis Chronic drug therapy- glucocorticoids,
thiazides, protease inhibitors
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Type 4 DM
Gestational diabetes mellitus Last trimester of pregnancy
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Glycosylated haemoglobin
Integrated measure of glycaemic control
Non-enzymatic glycosylation of proteins
Rate of glycosylation is directly proportional to glucose concentration
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Insulins use and charecteristics
Beef insulin Pork insulin Insulin by recombinant DNA
technology Human insulin
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Insulin
Proinsulin and insulin High molecular weight polypeptide Metabolism Degraded within the liver and kidneys� 80% metabolized in the liver-H.insulinase� Half-life of about 5 minutes� Degraded by hepatic glutathione insulin �
dehydrogenase Enzyme disrupts S-S bonds�
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Ultra short acting insulin
Insulin lispro Insuin aspart Insulin glulisine-CSII Rapid absorption from subcutaneous
tissue
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Short acting insulin
Regular insulin Prompt insulin-Zn suspension recombinant DNA tech NPH or isophane insulin
Intermediate acting insulin NPH or isophane insulin Rapid absorption and sustained
action
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Long acting insulin- not given IV
INSULIN GARGINE
Long acting insulin analogue
Soluble at pH 4
INSULIN DETRIMER
Has fatty acid side chain Slow and sustained release
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Therapeutic uses
Type 1 DM Diabetic keto acidosis Non-ketotic hyperglycemia
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Adverse effects
Hypoglyceminia Lipodystrophy Allergic manifestations Insulin resistance >100 units/day
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