1. Cellular Uptake of Glucose

4. –80-110 mg/dl euglycemia –< 45 mg/dl hypoglycemia –> 150-200 mg/dlafter CHO meal (ie, below T max ) –> 300-600 mg/dluncontrolled diabetes Cellular Uptake of Glucose 1.) Gradient usually exists ECF>ICF (HK keeps ICF low) 2.) Glucose is polar, therefore is hydrophilic Facilitated diffusion occurs via 5 glucose transporters GLUT 1  GLUT 5

5. Annimation of Glucose uptake

6. Kinetics of Facilitated Diffusion

7. –Based on concentration gradient Cellular Uptake of Glucose 3.) Unregulated glucose uptake –GLUT 1, 2, 3 & 5 (liver, neurons, RBC, kidney) 4.) Regulated glucose uptake –Insulin on GLUT 4 (muscle, adipose) 5.) Insulin -- Pancreas  cells –  &  Chains –3 disulfide bonds Insulin receptor -- membrane 4 subunits  GLUT 4 translocation from intracellular storage sites to membrane  glucose uptake 10-20x within 5 min.

8. Glucose Transport Proteins

9. GLUT Transporters: 1,2,3 & 5

11. Uniporter Symport Antiport Facilitated Diffusion

12. Insulin A chain 21AA B chain 30AA S S S S Insulin Receptor SS B Subunits A Subunits Tyrosine Kinase (Autophosphorylate) Fully active Tyrosine Kinase now can phosphorylate (activate/deactivate) intracellular enzymes Activates PDE cAMP activates PP-1 / dephosphorylates GS and PKA EPI inhibits insulin receptor and release

17. CP and ATP Use During Exercise Myokinase reaction 2 ADP ATP + AMP

18. Changes in ATP,ADP and AMP

21. Glucose 4 Transporter Ca ++ activated GLUT-4 transporters are from a different pool, located near triad. Insulin and contraction have additive effects on glucose uptake AMP AMP Kinase

22. The Insulin Receptor and Regulation of Blood Glucose

23. Receptors

24. cAMP-Dependent Protein Kinase Regulation of Glycogen Metabolism

25. Glucose Transporters