Pharm 6 Diabetes Flashcards
2 methods of insulin secretion
- Pulsatile pacemaker B cells open Ca channels
- Glucose through GLUT2 -> ATP -> block KIR channel -> Ca opens
Insulin molecule
A + B chain, C-peptide is cleaved
Insulin metabolism
50% degraded in liver, 50% in other target tissues
Insulin receptor MOA (GLUT4)
Tetramer
-Insulin binds to a-subunits -> b-subunits autophosphorylate -> tyrosine kinase
Insulin receptor MOA (mitogen)
MAP-kinase phosphorylation
Insulin in liver
- Glycogen/triglyceride synthesis
- Inhibit glycogenolysis/gluconeogenesis
Insulin in fat
- Glucose uptake, triglyceride storage
- Inhibit lipolysis
Insulin in general
Promote anabolism, inhibit catabolism
Insulin deficiency acidosis mechanism
Increase lipolysis -> ketoacids -> acidosis
Glucose intolerance with onset during pregnancy
GDM - Gestational Diabetes Mellitus
Instant type I diabetes cause
Total pancreatectomy
Drug therapy provoking chronic hyperglycemia
Steroid therapy
Rate limiting step for insulin absorption
Subcutaneous dissociation from hexamers into dimers and then monomers
-Lispro-
Lysine-Proline switched, can’t form aggregates
- Ultra fast
- Take after starting meal
-Aspart-
Proline replaced with aspartic acid, can’t form aggregates
-Ultra fast
-Insulin-
Can be given IV
-Fast
-NPH insulin-
Regular plus protamine zinc insulin (positively charged)
-Intermediate
-Glargine-
Ultra slow, peakless
-Single bedtime dose
-Determir-
Binds to albumin
-Ultra slow
Insulin pump benefit
Controls “dawn phenomenon”
Injection to accelerate insulin absorption
- Intramuscular
- Heat (exercise)
- Abdomen or buttock (blood flow)
Compromised renal function effect on insulin
Reduced clearance, prolonged effectiveness
-Pramlintide-
Amylin analog
- Slows postprandial glucose levels
- Slow stomach, inhibit glucagon
-Pramlintide-
Contraindications
Adverse Effects
- Gastroparesis
- Delayed onset of action of oral drugs